Chronic Kidney Disease (CKD) - At a Glance

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Information about Chronic Kidney Disease (CKD) - At a Glance
Health & Medicine

Published on November 26, 2013

Author: MohammedGawad

Source: slideshare.net

Description

by dr Mohammed Abel Gawad (drgawad@gmail.com): Nephrology Specialist at Kidney & Urology Center - Alexandria - Egypt. website: www.nephrotube.blogspot.com

Chronic Kidney Disease At a Glance Mohammed Abdel Gawad Nephrology Specialist Kidney & Urology Center (KUC) - Alexandria drgawad@gmail.com

CKD Definition, Diagnosis & Classification CKD Management

CKD Definition, Diagnosis & Classification

What is the definition of CKD? Abnormal Kidney or Kidney structure function for > 3 months with implications for health.

What is the definition of CKD? Abnormal Kidney or Kidney structure function for > 3 months with implications for health.

What is the definition of CKD? Abnormal Kidney or Kidney structure function for > 3 months with implications for health.

Causes of CKD

Causes of CKD - USA

Causes of CKD - EGYPT DM Hypertension Chronic glomerulonephritis Chronic pyelonephritis CVD and its related risk factors (e.g. obesity, smoking) Analgesics abuse Renal stones & Obstructive uropathy APKD AKI Many cases the cause is unknown

CKD Classification What is GFR?

CKD Classification What is GFR? Glomerular Filtration Tubular Reabsorption Tubular Secretion Excretion

CKD Classification What is GFR? Glomerular Filtration Tubular Reabsorption Tubular Secretion Excretion GFR: The quantity of glomerular filtrate formed in all nephrons of both kidneys / min.

CKD Classification What is GFR? Glomerular Filtration Tubular Reabsorption Tubular Secretion Excretion GFR: The quantity of glomerular filtrate formed in all nephrons of both kidneys / min.

CKD Classification How GFR is Estimated or Measured? Estimation &/or Measurement of GFR Exogenous Filtration Markers Inulin, iothalamate, EDTA, diethylene triamine pentaacetic acid, iohexol Endogenous Filtration Markers Creatinine Clearance (CrCl) eGFR equations (age, sex, race, and body size, in addition to serum creatinine, cystatin)

CKD Classification How GFR is Estimated or Measured? Estimation &/or Measurement of GFR Exogenous Filtration Markers Inulin, iothalamate, EDTA, diethylene triamine pentaacetic acid, iohexol Endogenous Filtration Markers Creatinine Clearance (CrCl) eGFR equations (age, sex, race, and body size, in addition to serum creatinine, cystatin)

CKD Classification How GFR is Estimated or Measured? Estimation &/or Measurement of GFR Exogenous Filtration Markers Endogenous Filtration Markers Inulin, iothalamate, EDTA, diethylene triamine pentaacetic acid, iohexol Creatinine Clearance (CrCl) eGFR equations (age, sex, race, and body size, in addition to serum creatinine, cystatin)

CKD Classification How GFR is Estimated or Measured? Estimation &/or Measurement of GFR Exogenous Filtration Markers Endogenous Filtration Markers Complicated & Costy eGFR is not Measured GFR Inulin, iothalamate, EDTA, diethylene triamine pentaacetic acid, iohexol Creatinine Clearance (CrCl) eGFR equations (age, sex, race, and body size, in addition to serum creatinine, cystatin)

CKD Classification How GFR is Estimated or Measured? Cystatin C • It is found in virtually all tissues and body fluids. • It is a potent inhibitor of lysosomal proteinases (enzymes from a special subunit of the cell that break down proteins) • One of the most important extracellular inhibitors of cysteine proteases (it prevents the breakdown of proteins outside the cell by a specific type of protein degrading enzymes)

CKD Classification eGFR Equations

CKD Classification eGFR Equations The recommended equations by KDIGO 2012 to be used to eGFR

CKD Classification eGFR Equations Limitations It depends on Cr serum level (affected by other factors)

CKD Classification eGFR Equations Limitations It depends on serum Cystatin C (affected by other factors)

CKD Classification eGFR Equations Limitations • Under or over-estimates GFR in certain GFR ranges and age groups. eGFR is not Measured GFR

CKD Classification eGFR Equations Limitations eGFR equations are not 100% accurate in estimation of actual GFR. eGFR is not Measured GFR

CKD Classification KDIGO 2012

CKD Classification KDIGO 2012

CKD Classification KDIGO 2012 Albuminuria and Proteinuria are corner stones in classification of all stages of CKD beside eGFR

CKD Classification KDIGO 2012 Albuminuria and Proteinuria are corner stones in classification of all stages of CKD beside eGFR CGA Classification (Cause, GFR, Albuminuria) Also mention the cause when classifying CKD

CKD Classification KDIGO 2012 Albuminuria and Proteinuria are corner stones in classification of all stages of CKD beside eGFR The term micro or macro albuminuria no longer be used CGA Classification (Cause, GFR, Albuminuria) Also mention the cause when classifying CKD

Why should proteinuria be added to CKD Classification? The Lancet, vol 375, Matshushita K, van de Velde M, Astor BC, et al.

How should proteinuria be measured? Test Comments Urine dipstick semiquantitative 24-hour urine collection (PER, AER) • cumbersome, • often inaccurate or incomplete PCR • most useful for monitoring of proteinuria • a first morning void is most reliable ACR • most useful for monitoring of albuminuria • a first morning void is most reliable

How should proteinuria be measured?

What are the limitations of albuminuria measurement?

How does CKD present? Asymptomatic Disease Especially early despite the accumulation of harmful metabolites Incidental finding of urine abnormalities or raised creatinine Is there a role for CKD Screening Programs? Whom to screen?

How does CKD present? Asymptomatic Disease Especially early despite the accumulation of harmful metabolites Incidental finding of urine abnormalities or raised creatinine Is there a role for CKD Screening Programs? Whom to screen? Non Specific S&S

CKD Definition, Diagnosis & Classification CKD Management

CKD Management

Management of CKD Complications Prevention of CKD Progression CKD Management

Management of CKD Complications CKD Management

CKD Complications & Management Mineral and bone disorder (MBD) Anemia Cardiovascular disease Acidosis Drug Dosing Malnutrition Infection & Immunization

CKD Complications & Management Anemia

Anemia in CKD Back to Basics (1) – Erythropoietin Hormone Hypoxia M.Gawad. www.nephrotube.blogspot.com

Anemia in CKD Back to Basics (1) – Erythropoietin Hormone Hypoxia 90% 10% Erythropoietin M.Gawad. www.nephrotube.blogspot.com

Anemia in CKD Back to Basics (1) – Erythropoietin Hormone Hypoxia 90% 10% Erythropoietin M.Gawad. www.nephrotube.blogspot.com

Anemia in CKD Back to Basics (1) – Erythropoietin Hormone Increase RBCs formation & Correct Hypoxia Hypoxia 90% 10% Erythropoietin M.Gawad. www.nephrotube.blogspot.com

Anemia in CKD Pathogenesis (1) Decrease RBCs life span, blood sampling, blood loss during haemodialysis Erythropoietin deficiency Increase RBCs formation & Correct Hypoxia Hematinic deficiency (back to basics 2) Hypoxia 90% 10% Erythropoietin • BM fibrosis (↑PTH) • BM affected by retained toxins M.Gawad. www.nephrotube.blogspot.com

Anemia in CKD Back to Basics (2) – RBCs Formation

Anemia in CKD Back to Basics (2) – RBCs Formation

Anemia in CKD Back to Basics (2) – RBCs Formation

Anemia in CKD Pathogenesis (2) - Hematinic Deficiency

Anemia in CKD – Management General Steps Step 1: Step 2: Iron Status & Initial Evaluation ESA Therapy

Anemia in CKD – Management Step1: Iron Status & Initial Evaluation Step 1: Iron Status & Initial Evaluation

Anemia in CKD – Management Step1: Iron Status & Initial Evaluation Anemia of CKD? Step 1: Iron Status & Initial Evaluation • Normochromic Normocytic • Hypochromic Microcytic • Normochromic Macrocytic

Anemia in CKD – Management Step1: Iron Status & Initial Evaluation Anemia of CKD? Step 1: Iron Status & Initial Evaluation • Normochromic Normocytic • Hypochromic Microcytic • Normochromic Macrocytic Presence of other type of anemia may point to another cause rather than CKD (on top of CKD)

Anemia in CKD – Management Step1: Iron Status & Initial Evaluation + other Investigations • CHr • CRP • Occult blood in stool • Blood film Step 1: Iron Status & Initial Evaluation

Anemia in CKD – Management Step 1: Iron Therapy When to start? TSAT is  30% ferritin  500 ng/ml

Anemia in CKD – Management Step 1: Iron Therapy Oral vs IV iron? Not on HD On HD Try oral iron IV iron is mandatory

Anemia in CKD – Management Step 1: Iron Therapy Available IV iron therapy Scott B. et al. American Journal of Hematology 76:74–78 (2004)

Anemia in CKD – Management Step 1: Iron Therapy Available IV iron therapy So IV iron sensitivity test is always required before IV dextran Scott B. et al. American Journal of Hematology 76:74–78 (2004)

Anemia in CKD – Management Step 1: Iron Therapy What is the IV iron protocol in CKD patients? Initial loading (large) dose Subsequent maintenance (small) doses Follow up iron profile (TSAT, ferritin, CHr)

Anemia in CKD – Management General Steps Step 1: Step 2: Iron Status & Initial Evaluation ESA Therapy

Anemia in CKD – Management General Steps Step 2: ESA Therapy

Anemia in CKD – Management Step 2: ESA Therapy Protocol Initiation Maintenance

Anemia in CKD – Management Step 2: ESA Therapy Protocol Initiation Maintenance

Anemia in CKD – Management Step 2: ESA Therapy Hb Target 10 – 11.5 g/dl Individualization (Some patients have improved QOL with higher Hb level > 11.5g/dl) In all adults not >13

Anemia in CKD – Management Step 2: ESA Therapy Available ESAs, dosing & route of administration Initiation Dose CKD ND EPO Darbepoetin alfa Methoxy polyethylene glycol-epoetin beta Initiation Dose CKD 5HD 20-50 units/kg 3 times/week (I.V. dosage must be 20-30% higher than S.C. dosage) 0.45 g/kg every four weeks (S.C. or IV) 0.45 g/kg once weekly or 0.75 g/kg once every two weeks (S.C. or IV) 0.6mcg (600ng)/kg every two weeks (S.C. or IV)

Anemia in CKD – Management Step 2: ESA Therapy Available ESAs, dosing & route of administration Initiation Dose CKD ND EPO Darbepoetin alfa Methoxy polyethylene glycol-epoetin beta Initiation Dose CKD 5HD 20-50 units/kg 3 times/week (I.V. dosage must be 20-30% higher than S.C. dosage) 0.45 g/kg every four weeks (S.C. or IV) 0.45 g/kg once weekly or 0.75 g/kg once every two weeks (S.C. or IV) 0.6mcg (600ng)/kg every two weeks (S.C. or IV)

Anemia in CKD – Management Step 2: ESA Therapy • What is the target Hb level for renal patients? 1. 11.5 - 13 g/dl. 2. 10 – 11.5 g/dl. 3. None of the above.

Anemia in CKD – Management Step 2: ESA Therapy • What is the target Hb level for renal patients? 1. 11.5 - 13 g/dl. 2. 10 – 11.5 g/dl. Don’t forget Individualization 3. None of the above.

Anemia in CKD – Management Step 2: ESA Therapy ESA Hyporesponsivness Treat Ix Hyporesponsivness to ESA therapy

Anemia in CKD – Management Step 2: ESA Therapy ESA Hyporesponsivness • CHr • CRP • Occult blood in stool • Blood film Treat Ix Hyporesponsivness to ESA therapy

Anemia in CKD – Management Step 2: ESA Therapy • CHr • CRP • Occult blood in stool • Blood film Hb Response ESA Hyporesponsivness Plateau Effect Due to Fe ↓ 2nry to ESA administration Treat Time Ix Hyporesponsivness to ESA therapy

Anemia in CKD – Management Step 2: ESA Therapy ESA Side Effects Influenza-like syndrome (affecting 5 %)* Unknown etiology** Respond to antiinflammatory drugs** *Bennett WM. J Am Soc Nephrol 1991; 1:990. ** Buur T etal. Clin Nephrol 1990; 34:230.

Anemia in CKD – Management Step 2: ESA Therapy ESA Side Effects Influenza-like syndrome (affecting 5 %)* Hypertension Unknown etiology** Respond to antiinflammatory drugs** *Bennett WM. J Am Soc Nephrol 1991; 1:990. ** Buur T etal. Clin Nephrol 1990; 34:230.

Anemia in CKD – Management Step 2: ESA Therapy ESA Side Effects Influenza-like syndrome (affecting 5 %)* Hypertension Unknown etiology** Pure red cell aplasia (PCR) Respond to antiinflammatory drugs** Human serum albumin is used as a stabilizing agent in many EPO preparations, although polysorbate was used with Eprex which stimulate the formation of EPO-Ab *Bennett WM. J Am Soc Nephrol 1991; 1:990. ** Buur T etal. Clin Nephrol 1990; 34:230.

Anemia in CKD – Management Step 2: ESA Therapy ESA Side Effects Influenza-like syndrome (affecting 5 %)* Hypertension Unknown etiology** Pure red cell aplasia (PCR) Respond to antiinflammatory drugs** Human serum albumin is used as a stabilizing agent in many EPO preparations, although polysorbate was used with Eprex which stimulate the formation of EPO-Ab *Bennett WM. J Am Soc Nephrol 1991; 1:990. ** Buur T etal. Clin Nephrol 1990; 34:230.

Anemia in CKD – Management Blood Transfusion When managing chronic anemia, we recommend avoiding, when possible, red cell transfusions to minimize the general risks related to their use. In patients eligible for organ transplantation, we specifically recommend avoiding, when possible, red cell transfusions to minimize the risk of allosensitization. Benefits of red cell transfusions may outweigh the risks in patients in whom: 1. ESA therapy is ineffective (e.g., hemoglobinopathies, bone marrow failure, ESA resistance) 2. The risks of ESA therapy may outweigh its benefits (e.g., previous or current malignancy, previous stroke)

CKD Complications & Management Mineral and bone disorder (MBD) Anemia Cardiovascular disease Acidosis Drug Dosing Malnutrition Infection & Immunization

CKD Complications & Management Mineral and bone disorder (MBD)

Mineral & Bone Disorder (MBD) General Definition PTH – Vit D – Ca – Pi Axis Mineral and bone disorder (MBD)

Mineral & Bone Disorder (MBD) General Definition PTH – Vit D – Ca – Pi Axis Mineral and bone disorder (MBD)

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (1) : PTH – Vit D – Ca – Pi Axis PTH Increase serum Pi Increase serum Ca M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (1) : PTH – Vit D – Ca – Pi Axis PTH Increase serum Pi Increase serum Ca Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com Decrease serum Pi

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (1) : PTH – Vit D – Ca – Pi Axis PTH Action: increase serum Ca and decrease serum Pi PTH So low serum Ca & high serum Pi will stimulate PTH release & vise verca Increase serum Pi Increase serum Ca Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com Decrease serum Pi

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (1) : PTH – Vit D – Ca – Pi Axis Vit D PTH Increase serum Pi Calcidiol 25-OH-D Increase serum Ca Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com Decrease serum Pi

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (1) : PTH – Vit D – Ca – Pi Axis Vit D PTH Increase serum Pi Calcidiol 25-OH-D α1 hydroxylase Increase serum Ca Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com Decrease serum Pi

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (1) : PTH – Vit D – Ca – Pi Axis Vit D PTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase Increase serum Pi Increase serum Ca Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com Decrease serum Pi

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (1) : PTH – Vit D – Ca – Pi Axis Vit D PTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase Increase serum Pi Increase serum Ca Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com Decrease serum Pi

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (1) : PTH – Vit D – Ca – Pi Axis Vit D Increase Ca & Pi reabsorption Calcidiol 25-OH-D PTH Calcitriol 1,25-(OH)2-D α1 hydroxylase Increase serum Pi Increase serum Ca Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com Decrease serum Pi

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (1) : PTH – Vit D – Ca – Pi Axis Active vit D Action: Vit D Increase Ca & Pi reabsorption Calcidiol 25-OH-D PTH Calcitriol 1,25-(OH)2-D α1 hydroxylase increase serum Ca & Pi Increase serum Pi Increase serum Ca Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com Decrease serum Pi

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : PTH – Vit D – Ca – Pi Axis Vit D Increase Ca & Pi reabsorption Calcidiol 25-OH-D PTH Calcitriol 1,25-(OH)2-D α1 hydroxylase Increase serum Pi Increase serum Ca Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com Decrease serum Pi

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : PTH – Vit D – Ca – Pi Axis Vit D PTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : PTH – Vit D – Ca – Pi Axis Vit D PTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : PTH – Vit D – Ca – Pi Axis Vit D 2ry hyperPTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase PTH Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : PTH – Vit D – Ca – Pi Axis Bone Disease Fractures Bone pain Marrow fibrosis Erythropoietin resistance Vit D 2ry hyperPTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase PTH Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : Tertiary Hyperparathyroidism PTH Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : Tertiary Hyperparathyroidism PTH Persistent untreated Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : Tertiary Hyperparathyroidism Persistent parathyroid stimulation PTH Persistent untreated Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : Tertiary Hyperparathyroidism Persistent parathyroid stimulation Formation of parathyroid adenoma PTH Persistent untreated Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : Tertiary Hyperparathyroidism Persistent parathyroid stimulation Formation of parathyroid adenoma PTH Persistent untreated Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (1) : Tertiary Hyperparathyroidism Persistent parathyroid stimulation Formation of parathyroid adenoma Increase serum Pi & Ca PTH Persistent untreated Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion M.Gawad. www.nephrotube.blogspot.com

Mineral & Bone Disorder (MBD) Lab Abnormalities Summary PTH Ca Pi ALK Phosphatase Secondary Hyperparathyroidism ↑ ↓ ↑ ↑ Tertiary Hyperparathyroidism ↑↑↑ ↑ ↑↑ ↑

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (2): FGF 23 Vit D 2ry hyperPTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase PTH Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (2): FGF 23 Vit D 2ry hyperPTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase PTH Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (2): FGF 23 Fibroblast Growth Factor 23 (FGF 23) Vit D 2ry hyperPTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase PTH Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion

Mineral & Bone Disorder (MBD) Lab Abnormalities Back to Basics (2): FGF 23 Fibroblast Growth Factor 23 (FGF 23) Vit D 2ry hyperPTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase PTH Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (2): FGF 23 Fibroblast Growth Factor 23 (FGF 23) in CKD Vit D PTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (2): FGF 23 Fibroblast Growth Factor 23 (FGF 23) in CKD Vit D PTH Calcidiol 25-OH-D Calcitriol 1,25-(OH)2-D α1 hydroxylase Still ↑ Pi serum level Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion

Mineral & Bone Disorder (MBD) Lab Abnormalities Pathogenesis (2): FGF 23 in CKD Persistent very high level of FGF 23 in CKD Vit D Calcidiol 25-OH-D Fibroblast Growth Factor 23 (FGF 23) Calcitriol 1,25-(OH)2-D Strong independent predictor of mortality in CKD α1 hydroxylase Still ↑ Pi serum level PTH Decrease serum Ca Increase serum Pi Increase Ca reabsorption Increase Pi excretion

Mineral & Bone Disorder (MBD) General Definition PTH – Vit D – Ca – Pi Axis Mineral and bone disorder (MBD)

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy Back to Basics – TMV Classification System Turnover High Normal Low Mineralization Normal Abnormal Volume High Normal Low

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy Spectrum iPTH < 50 pg/ml Low turn over bone disease iPTH 150-300 pg/ml Normal bone formation iPTH > 300 pg/ml High turn over bone disease (Ostetis fibrosa cystica) Mixed lesion KEITH A et al. July 20, 1995. Vol. 333 No. 3

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy High turn over - Osteitis Fibrosa Cystica Increased bone resorption and formation Increased numbers of osteoclasts and osteoblasts iPTH 150-300 pg/ml Increased of woveniPTH and peritrabecular bone, fibrosis. < 50 pg/ml Low turn over bone disease Normal bone formation iPTH > 300 pg/ml High turn over bone disease (Ostetis fibrosa cystica) Mixed lesion KEITH A et al. July 20, 1995. Vol. 333 No. 3

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy High turn over - Osteitis Fibrosa Cystica

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy High turn over - Osteitis Fibrosa Cystica

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy High turn over - Osteitis Fibrosa Cystica Salt & Pepper Appearance

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy High turn over - Osteitis Fibrosa Cystica Rugger jersey Spine

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy High turn over - Osteitis Fibrosa Cystica

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy High turn over - Osteitis Fibrosa Cystica

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy High turn over - Osteitis Fibrosa Cystica Clinically Bone fractures Bone pain and discomfort Metastatic calcification

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy Low turn over – Adynamic Bone Disease iPTH < 50 pg/ml Low turn over bone disease iPTH 150-300 pg/ml iPTH > 300 pg/ml low or Normal bone absent bone formation High turn over formation bone disease paucity of bone-forming osteoblasts and (Ostetis fibrosa bone-resorbing osteoclasts. cystica) Mixed lesion KEITH A et al. July 20, 1995. Vol. 333 No. 3

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy Low turn over – Adynamic Bone Disease What is the cause?? 1- In the past it was attributed to Al toxicity 2- Over treated hyperparathyroidism iPTH < 50 pg/ml Low turn over bone disease iPTH 150-300 pg/ml iPTH > 300 pg/ml low or Normal bone absent bone formation High turn over formation bone disease paucity of bone-forming osteoblasts and (Ostetis fibrosa bone-resorbing osteoclasts. cystica) Mixed lesion KEITH A et al. July 20, 1995. Vol. 333 No. 3

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy Low turn over – Adynamic Bone Disease What is the cause?? 1- In the past it was attributed to Al toxicity 2- Over treated hyperparathyroidism iPTH < 50 pg/ml Low turn over bone disease Laboratory?? Low PTH Low ALK Phosphatase High Ca & Pi iPTH High incidence > 300 pg/ml iPTHtissue of 150-300 pg/ml calcification low or Normal bone absent bone formation High turn over formation bone disease paucity of bone-forming osteoblasts and (Ostetis fibrosa bone-resorbing osteoclasts. cystica) Mixed lesion KEITH A et al. July 20, 1995. Vol. 333 No. 3

Mineral & Bone Disorder (MBD) Bone Abnormalities – Renal Osteodystrophy Spectrum S Moe et al. Kidney International (2006) 69, 1945–1953

Mineral & Bone Disorder (MBD) General Definition PTH – Vit D – Ca – Pi Axis Mineral and bone disorder (MBD)

Mineral & Bone Disorder (MBD) Ca-Phosphate Product PTH – Vit D – Ca – Pi Axis ↑ Ca X Pi Deposition of Ca & Pi 1- Vascular, articular, and extra-articular soft tissue 2- Pruritis (deposition under skin)

Mineral & Bone Disorder (MBD) Vascular & Soft tissue Classification PTH – Vit D – Ca – Pi Axis

Mineral & Bone Disorder (MBD) Management – Biochemical Targets

Mineral & Bone Disorder (MBD) Management – Drugs Used 1- Phosphate binders. 2- Vit D and Vit D analogues. 3- Cinacalcet.

Mineral & Bone Disorder (MBD) Management – Drugs 1- Phosphate binders. 2- Vit D and Vit D analogues. 3- Cinacalcet.

Mineral & Bone Disorder (MBD) Management – Drugs Phosphate Binders

Mineral & Bone Disorder (MBD) Management – Drugs Phosphate Binders

Mineral & Bone Disorder (MBD) Management – Drugs Phosphate Binders

Mineral & Bone Disorder (MBD) Management – Drugs Used 1- Phosphate binders. 2- Vit D and Vit D analogues. 3- Cinacalcet.

Mineral & Bone Disorder (MBD) Management – Drugs Used 1- Phosphate binders. 2- Vit D and Vit D analogues. 3- Cinacalcet.

Mineral & Bone Disorder (MBD) Management – Drugs Vitamin D & Vit D Analogues

Mineral & Bone Disorder (MBD) Management – Drugs Vitamin D & Vit D Analogues Liver

Mineral & Bone Disorder (MBD) Management – Drugs Vitamin D & Vit D Analogues

Mineral & Bone Disorder (MBD) Management – Drugs Used 1- Phosphate binders. 2- Vit D and Vit D analogues. 3- Cinacalcet.

Mineral & Bone Disorder (MBD) Management – Drugs Used 1- Phosphate binders. 2- Vit D and Vit D analogues. 3- Cinacalcet.

Mineral & Bone Disorder (MBD) Management – Drugs Cinacalcet

Mineral & Bone Disorder (MBD) Management – Follow Up

Mineral & Bone Disorder (MBD) Management – Follow Up Therapeutic decisions must base on trends rather than on a single laboratory value.

Mineral & Bone Disorder (MBD) Management – Follow Up Therapeutic decisions must base on trends rather than on a single laboratory value. It is reasonable to base the frequency of monitoring on the presence and magnitude of abnormalities, and the rate of progression of CKD and also to monitor for trends and treatment efficacy and side-effects

Mineral & Bone Disorder (MBD) Management

CKD Complications & Management Mineral and bone disorder (MBD) Anemia Cardiovascular disease Acidosis Drug Dosing Malnutrition Infection & Immunization

CKD Complications & Management Cardiovascular disease

Chronic Cardio-Renal Syndrome

Cardio-Kidney-Damage El Nahas, KI 2010 Kidney International 78, 14-18 (July (1) 2010)

Heart & Kidney For good cardiac condition there must be a good renal condition. For good renal condition there must be a good cardiac condition.

CKD Complications & Management Mineral and bone disorder (MBD) Anemia Cardiovascular disease Acidosis Drug Dosing Malnutrition Infection & Immunization

CKD Complications & Management Malnutrition

CKD & Malnutrition Why CKD patients are malnourished? Decreased intake; loss of appetite Chronic inflammation: malnutrition-inflammationatherosclerosis (MIA) syndrome Resistance to anabolic hormones such as insulin and GH Decreased absorption Cytokines release and complement activation during haemodialysis Metabolic acidosis Diet restriction: e.g., low phosphate diet may lead to protein malnourishment

CKD & Malnutrition How can I minimize and treat malnutrition in CKD? Prevention of low-protein or low-calorie diets Correction of underlying infections or inflammatory processes Correction of anemia Control of metabolic acidosis Optimization of dialysis

CKD Complications & Management Mineral and bone disorder (MBD) Anemia Cardiovascular disease Acidosis Drug Dosing Malnutrition Infection & Immunization

CKD Complications & Management Acidosis

CKD & Acidosis Pathogenesis Normal Acid Base

CKD & Acidosis Pathogenesis Normal Acid Base

CKD & Acidosis Pathogenesis Normal Acid Base Reclamation & formation of HCO3

CKD & Acidosis Pathogenesis Normal Acid Base Reclamation & formation of HCO3

CKD & Acidosis Pathogenesis CKD – Metabolic Acidosis Reclamation & formation of HCO3

CKD & Acidosis Pathogenesis CKD – Metabolic Acidosis Reclamation & formation of HCO3

CKD & Acidosis Pathogenesis CKD – Metabolic Acidosis Reclamation & formation of HCO3

CKD & Acidosis Pathogenesis CKD – Metabolic Acidosis Reclamation & formation of HCO3

CKD & Acidosis Pathogenesis

CKD & Acidosis Management When is the drug to be used? Oral HCO3 (unless contraindicated) When to start HCO3 therapy? When serum HCO3 < 22 mmol/L What is the therapy target? Maintain serum HCO3 within normal

CKD Complications & Management Mineral and bone disorder (MBD) Anemia Cardiovascular disease Acidosis Drug Dosing Malnutrition Infection & Immunization

CKD Complications & Management Drug Dosing

CKD & Drug Dosing

CKD Complications & Management Mineral and bone disorder (MBD) Anemia Cardiovascular disease Acidosis Drug Dosing Malnutrition Infection & Immunization

CKD Complications & Management Infection & Immunization

Infection & Immunization

Management of CKD Complications Prevention of CKD Progression CKD Management

Prevention of CKD Progression CKD Management

Why it is important to delay CKD progression? Prevention of CKD Progression Matshushita K et al. The Lancet, vol 375, p. 2073-2081, 2010, Kidney International. Levey AS, de Jong PE, Coresh J, et al.

How to prevent CKD progression? Glycemic control BP control & Proteinuria Diet Hyperuricemia Hyperlipidemia Prevention of CKD Progression

How to prevent CKD progression? Glycemic control Prevention of CKD Progression

Glycemic Control in CKD Target HbA1c

Glycemic Control in CKD Target HbA1c

Glycemic Control in CKD Target HbA1c

Glycemic Control in CKD Target HbA1c

Glycemic Control in CKD Target HbA1c

How to prevent CKD progression? Glycemic control BP control & Proteinuria Diet Hyperuricemia Hyperlipidemia Prevention of CKD Progression

How to prevent CKD progression? BP control & Proteinuria Prevention of CKD Progression

Blood Pressure Control in CKD Why to treat HTN in CKD? HTN is a precipitating & initiating factor of CKD El Nahas, KI 2010 Kidney International 78, 14-18 (July (1) 2010)

Blood Pressure Control in CKD Why to treat HTN in CKD? HTN is a prognostic marker for CKD progression Bakris et al. American Journal of Kidney Diseases, Vol 36, No 3 (September), 2000: pp 646-661

Proteinuria & CKD Why Proteinuria is an important issue? Relationship Between Baseline Proteinuria and Subsequent GFR Decline J Am Soc Nephrol. 2003;14:3217-3232

Blood Pressure Control in CKD Life Style

Blood Pressure & Proteinuria Control in CKD When to start anti-HTN therapy? When to start?

Blood Pressure & Proteinuria Control in CKD When to start anti-HTN therapy? When to start?

Blood Pressure & Proteinuria Control in CKD When to start anti-HTN therapy? When to start?

Blood Pressure & Proteinuria Control in CKD When to start anti-HTN therapy? There is insufficient evidence to recommend combining an ACE-I with ARBs to prevent progression of CKD. When to start?

Blood Pressure & Proteinuria Control in CKD When to start anti-HTN therapy? There is insufficient evidence to recommend combining an ACE-I with ARBs to prevent progression of CKD.

Blood Pressure & Proteinuria Control in CKD Mechanism of action of ACE-I & ARBs? Afferent Arteriole Efferent Arteriole M.Gawad. www.nephrotube.blogspot.com

Blood Pressure & Proteinuria Control in CKD Mechanism of action of ACE-I & ARBs? In HTN & CKD Afferent Arteriole ↑ Intraglomerular Pressure Efferent Arteriole M.Gawad. www.nephrotube.blogspot.com

Blood Pressure & Proteinuria Control in CKD Mechanism of action of ACE-I & ARBs? In HTN & CKD Afferent Arteriole ↑ Intraglomerular Pressure Efferent Arteriole M.Gawad. www.nephrotube.blogspot.com

Blood Pressure & Proteinuria Control in CKD Mechanism of action of ACE-I & ARBs? In HTN & CKD Afferent Arteriole ↑ Intraglomerular Pressure Efferent Arteriole ACE-I & ARBs M.Gawad. www.nephrotube.blogspot.com

Blood Pressure & Proteinuria Control in CKD Mechanism of action of ACE-I & ARBs? In HTN & CKD Afferent Arteriole ↑ Intraglomerular Pressure Efferent Arteriole ACE-I & ARBs M.Gawad. www.nephrotube.blogspot.com

Blood Pressure & Proteinuria Control in CKD Mechanism of action of ACE-I & ARBs? In HTN & CKD Afferent Arteriole ↓ Intraglomerular Pressure Efferent Arteriole ACE-I & ARBs M.Gawad. www.nephrotube.blogspot.com

Blood Pressure & Proteinuria Control in CKD Mechanism of action of ACE-I & ARBs? In HTN & CKD Afferent Arteriole ↓ Intraglomerular Pressure Efferent Arteriole ACE-I & ARBs M.Gawad. www.nephrotube.blogspot.com

Blood Pressure & Proteinuria Control in CKD When to start anti-HTN therapy?? When to start? What is the target of BP in CKD?

Blood Pressure & Proteinuria Control in CKD What is the target of BP in CKD?

Blood Pressure & Proteinuria Control in CKD What is the target of BP in CKD?

How to prevent CKD progression? Glycemic control BP control & Proteinuria Diet Hyperuricemia Hyperlipidemia Prevention of CKD Progression

How to prevent CKD progression? Prevention of CKD Progression Diet

Diet Recommendations

Diet - Phosphorus Intake

Diet - Phosphorus Intake Drugs & HD are not sufficient alone for Pi reduction Diet has an important role in Pi reduction

Diet - Protein Intake Recommended Intake Protein Intake GFR < 30 ml/min in diabetics (2C) & non diabetics (2B) Protein intake 0.8 g/kg/day Adults with CKD at risk of progression Avoid high protein intake (>1.3 g/kg/day) (2C)

Diet - Protein Intake Recommended Intake Protein Intake GFR < 30 ml/min in diabetics (2C) & non diabetics (2B) Protein intake 0.8 g/kg/day Adults with CKD at risk of progression Avoid high protein intake (>1.3 g/kg/day) (2C)

Diet - Protein Intake Recommended Intake

Diet - Protein Intake Why to restrict protein intake? Reduction of accumulation of metabolic waste products & uremic toxins The role of dietary protein restriction in slowing progression of CKD is more controversial

Dose low protein diet slow CKD progression? What is the available evidence? Think Critically

Dose low protein diet slow CKD progression? What is the available evidence? When criticizing an evidence about low protein diet & CKD progression, check the following points Number of patients in the study Duration of the study follow up Controlling of other risk factors The duration of causative factor of CKD How renal function is assessed?

Dose low protein diet slow CKD progression? What is the available evidence? There is no convincing or conclusive evidence that long-term protein restriction delays the progression of CKD.

Kasiske BL et al. Am J Kidney Dis 1998; 31: 954–961.

Kasiske BL et al. Am J Kidney Dis 1998; 31: 954–961.

Compared the effects of LPD and BP control on the progression of CKD in over 800 subjects Mean follow-up was 2.2 years Study A Study B 585 patient mGFR of 25-55 ml/min/1.73 m2 255 patients mGFR 13-24 ml/min/1.73 m2 DPIs 1.11 g/kg/day LDPIs 0.73 g/kg/day LDPIs 0.69 g/kg/day LDPIs + KA 0.46 g/kg/day GFR loss was estimated by the slope of 125I-iothalamate clearance

Study A 585 patient mGFR of 25-55 ml/min/1.73 m2 DPIs 1.11 g/kg/day LDPIs 0.73 g/kg/day

585 patient mGFR of 25-55 ml/min/1.73 m2 DPIs 1.11 g/kg/day LDPIs 0.73 g/kg/day GFR Decline Study A

Study B 255 patients mGFR 13-24 ml/min/1.73 m2 LDPIs 0.69 g/kg/day LDPIs + KA 0.46 g/kg/day

Study B 255 patients mGFR 13-24 ml/min/1.73 m2 LDPIs 0.69 g/kg/day LDPIs + KA 0.46 g/kg/day

A follow-up study of the original MDRD Study followed those subjects recruited to Study B until the year 2000 Study B mGFR 13-24 ml/min/1.73 m2 LDPIs 0.69 g/kg/day LDPIs + KA 0.46 g/kg/day

A follow-up study of the original MDRD Study followed those subjects recruited to Study B until the year 2000 Study B mGFR 13-24 ml/min/1.73 m2 LDPIs 0.69 g/kg/day LDPIs + KA 0.46 g/kg/day

Compared the effects of LPD and BP control on the progression of CKD in over 800 subjects Mean follow-up was 2.2 years Study A Study B 585 patient mGFR of 25-55 ml/min/1.73 m2 255 patients mGFR 13-24 ml/min/1.73 m2 Usual DPIs 1.11 g/kg/day LDPIs 0.73 g/kg/day LDPIs 0.69 g/kg/day LDPIs + KA 0.46 g/kg/day GFR loss was estimated by the slope of 125I-iothalamate clearance

Compared the effects of LPD and BP control on the progression of CKD in over 800 subjects Mean follow-up was 2.2 years Study A Study B No significant differences in GFR decline, measured by 585 patient 255 patients mGFR of 25-55 ml/min/1.73 m2 125I-iothalamate clearance every 4 mGFR 13-24 ml/min/1.73 m2 months, were found between the diet groups in either study. Usual DPIs 1.11 g/kg/day LDPIs 0.73 g/kg/day LDPIs 0.69 g/kg/day LDPIs + KA 0.46 g/kg/day GFR loss was estimated by the slope of 125I-iothalamate clearance

4 small RCTs examining the effect of dietary protein restriction (0.6-0.8 g/kg/day) on CKD progression in adult patients with early (stages 2-3) CKD. (1-4) (1) Hansen HP et al. Kidney International. 2002; 62: 220-228. (2) Pijls LT et al. Journal of Clinical Nutrition. 2002; 56: 1200 - 1207. (3) Meloni C et al. Journal of Renal Nutrition. 2002; 12: 96 - 101. (4) Meloni et al. Journal of Renal Nutrition. 2004; 14: 208 - 213.

4 small RCTs examining the effect of dietary protein restriction (0.6-0.8 g/kg/day) on CKD progression in adult patients with early (stages 2-3) CKD. (1-4) None of the trials demonstrated a significant effect of dietary protein restriction on CKD progression, (except in a subgroup of 89 patients with nondiabetic early CKD). (4) (1) Hansen HP et al. Kidney International. 2002; 62: 220-228. (2) Pijls LT et al. Journal of Clinical Nutrition. 2002; 56: 1200 - 1207. (3) Meloni C et al. Journal of Renal Nutrition. 2002; 12: 96 - 101. (4) Meloni et al. Journal of Renal Nutrition. 2004; 14: 208 - 213.

High protein diet Ann Intern Med. 2003;138:460-467.

High protein diet Ann Intern Med. 2003;138:460-467.

Diet - Protein Intake What to take care from? Reverse Epidemiology (U-shaped Curve)

Diet - Protein Intake What to take care from? Reverse Epidemiology (U-shaped Curve) Recommended Protein intake leads to reduction of accumulation of uremic toxins

Diet - Protein Intake What to take care from? Reverse Epidemiology (U-shaped Curve) Insufficient protein intake may lead to loss of lean body mass, and malnutrition Recommended Protein intake leads to reduction of accumulation of uremic toxins

Diet - Protein Intake What to take care from? Reverse Epidemiology (U-shaped Curve) Insufficient protein intake may lead to loss of lean body mass, and malnutrition Excess dietary protein leads to the accumulation of uremic toxins & decrease GFR Recommended Protein intake leads to reduction of accumulation of uremic toxins M.Gawad. www.nephrotube.blogspot.com

Always talk with your patient about MALNUTRITION and its bad consequences

Low Protein Diet Evidence What We Miss? Large RCT for both diabetics & non diabetics, for long time for follow, up after controlling all precipitating parameters with recommended targets

How to prevent CKD progression? Glycemic control BP control & Proteinuria Diet Hyperuricemia Hyperlipidemia Prevention of CKD Progression

How to prevent CKD progression? Prevention of CKD Progression Hyperuricemia

Hyperuricemia When to start therapy?

Hyperuricemia When to start therapy?

How to prevent CKD progression? Glycemic control BP control & Proteinuria Diet Hyperuricemia Hyperlipidemia Prevention of CKD Progression

How to prevent CKD progression? Prevention of CKD Progression Hyperlipidemia

Newly CKD Lipid profile: Total chloesterol LDL HDL TG Detect 2ry causes: – smoking status – alcohol consumption – blood pressure – body mass index or other measure of obesity – fasting blood glucose – renal function - Nephrotic Syndrome – liver function (transaminases) No need for follow up – thyroid-stimulating hormone (TSH) if dyslipidaemia is present. - Medications

When to treat? Life style is mandatory in all stratigies if on dialysis if on statin or statin/ezetimibe if not on dialysis if not on statin or statin/ezetimibe Age: 18-49 Age: ≥50 Start Statins if: Continue Dont initiate - known coronary disease (myocardial infarction or coronary revascularization) GFR <60 GFR ≥60 Statin or statin/ezetimibe Statins - diabetes mellitus - prior ischemic stroke - estimated 10-year incidence of coronary death or non-fatal myocardial infarction > 10%

Timing of Initiation of RRT Dialysis

Timing of Initiation of RRT Transplantation

CKD NOC 2014 Registration is opened Contact: enquiries@globalkidneyacademy.co.uk

Thank You Gawad

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