1. Chronic Kidney Disease/Dialysis Belinda Jim, MD January 15, 2009

2. Definition NKF’s (National Kidney Foundation’s) K/DOQI (Kidney Disease Outcomes Quality Initiative) Work Group criteria for CKD are: NKF’s (National Kidney Foundation’s) K/DOQI (Kidney Disease Outcomes Quality Initiative) Work Group criteria for CKD are: Kidney damage for >3months, with or without decreased GFR manifest by either: Kidney damage for >3months, with or without decreased GFR manifest by either: Pathological abnormalities or Pathological abnormalities or Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in the imaging tests. Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in the imaging tests.OR GFR 3months GFR 3months

3. Causes of ESRD Regardless of acute or chronic, should calculate renal function by eGFR Regardless of acute or chronic, should calculate renal function by eGFR Used to evaluate extent of impairment, follow course of disease and response to therapy Used to evaluate extent of impairment, follow course of disease and response to therapy Dose adjustments Dose adjustments

4. Equations to Estimate GFR Gold Standard – inulin clearance, I-iothalmate, Tc- DTPA clearance. These tests are not uniform. Gold Standard – inulin clearance, I-iothalmate, Tc- DTPA clearance. These tests are not uniform. Cockcroft-Gault equation- Cockcroft-Gault equation- (140-age) x wt/ 72 x SCr. (x 0.85 for women). (140-age) x wt/ 72 x SCr. (x 0.85 for women). MDRD (Modification of Diet in Renal Disease) – Abbreviated version MDRD (Modification of Diet in Renal Disease) – Abbreviated version 186 x SCr. To power of -0.203 (x 0.742 if female) and (x1.210 if black). 186 x SCr. To power of -0.203 (x 0.742 if female) and (x1.210 if black). 24 hr. Urine for Cr.Cl – 24 hr. Urine for Cr.Cl – GFR = UCr.V/PCr x 0.70 (to convert to ml/min) GFR = UCr.V/PCr x 0.70 (to convert to ml/min)

5. CKD Staging and Prevalence CKD Stage GFR (mL/min/1.73 m 2 ) Number of Individuals 1  90 and evidence of kidney damage 5.6 million 2 60-89 and evidence of kidney damage 5.7 million 330-59 7.4 million 415-29300,000 5 <15 or dialysis 431,284 Coresh et al, J Am Soc Nephrol, 2005; 16: 180-188 Data supplied by USRDS 2004 Annual Data Report.

6. Natural History of Renal Disease Initial injury may vary in pathogenesis Initial injury may vary in pathogenesis Kidney adapts by increasing filtration rate in remaining normal nephrons  adaptive hyperfiltration Kidney adapts by increasing filtration rate in remaining normal nephrons  adaptive hyperfiltration Long-term damage, manifested by proteinuria and progressive renal insufficiency Long-term damage, manifested by proteinuria and progressive renal insufficiency Gradual decline usually asymptomatic Gradual decline usually asymptomatic No exact correlation between level of BUN and symptoms No exact correlation between level of BUN and symptoms Uremic symptoms: anorexia, nausea, vomiting, fatigue, hiccups, pruritis Uremic symptoms: anorexia, nausea, vomiting, fatigue, hiccups, pruritis

7. General Management Treatment of reversible causes Treatment of reversible causes Decreased renal perfusion Decreased renal perfusion Administration of nephrotoxic drugs Administration of nephrotoxic drugs Urinary tract obstruction Urinary tract obstruction Prevention or slow the progression Prevention or slow the progression Treatment of complications Treatment of complications Identification and adequate preparation of renal replacement therapy (RRT) Identification and adequate preparation of renal replacement therapy (RRT)

8. Factors Affecting Progression of CKD Non-Modifiable Risk Factors: Age – incidence climbs after 65 Age – incidence climbs after 65 Gender – more common in males with a faster rate of decline. Gender – more common in males with a faster rate of decline. Race – incidence higher in AA and Hispanics. Race – incidence higher in AA and Hispanics. Genetics – diabetic and non-diabetic nephropathies cluster in families. Genetics – diabetic and non-diabetic nephropathies cluster in families.

9. Modifiable Risk Factors Proteinuria – aim for <500mg/24hr. Proteinuria – aim for <500mg/24hr. Hypertension – aim for <130/80 or MAP <90 with ACE I/ARB. Hypertension – aim for <130/80 or MAP <90 with ACE I/ARB. Glycemic control – Evidence is conflicting in progression of CKD. Glycemic control – Evidence is conflicting in progression of CKD. Dyslipidemia – elevated levels associated with more rapid decline – esp in DN. Dyslipidemia – elevated levels associated with more rapid decline – esp in DN. Obesity - linked to faster rate of progression in CKD. Obesity - linked to faster rate of progression in CKD. Hyperuricemia – May cause renal injury and HTN through stimulation of renin-angiotensin system. Hyperuricemia – May cause renal injury and HTN through stimulation of renin-angiotensin system.

10. Treatment of Complications Volume overload Volume overload Hyperkalemia Hyperkalemia Metabolic acidosis Metabolic acidosis Hyperphosphatemia Hyperphosphatemia Anemia Anemia Hyperparathyroidism Hyperparathyroidism Bone disease Bone disease Uremic symptoms Uremic symptoms

11. Volume Overload Sodium and intravascular volume balance usually maintained until GFR falls below 10 to 15 ml/min Sodium and intravascular volume balance usually maintained until GFR falls below 10 to 15 ml/min Mild to moderate CKD less able to respond to rapid infusions of sodium, prone to overload Mild to moderate CKD less able to respond to rapid infusions of sodium, prone to overload Respond to combination of dietary sodium restriction and diuretic therapy Respond to combination of dietary sodium restriction and diuretic therapy

12. Hyperkalemia Problem with Problem with Aldosterone Aldosterone Distal flow in kidney (eGFR<10 -15ml/min). Distal flow in kidney (eGFR<10 -15ml/min). Patient is either: Patient is either: Oliguric. Oliguric. Has high K diet. Has high K diet. Has increased tissue breakdown. Has increased tissue breakdown. Has Hypoaldosteronism (eg. ACE Inhibitors, type IV RTA). Has Hypoaldosteronism (eg. ACE Inhibitors, type IV RTA). Treatment consists of low K diet (2gm/day), diuretics and kayexalate. Treatment consists of low K diet (2gm/day), diuretics and kayexalate.

13. Ion transport in collecting tubule cell

14. Metabolic Acidosis Increasing tendency to retain H + Increasing tendency to retain H + Decreased HCO3 -, usually between 12-20meq/L Decreased HCO3 -, usually between 12-20meq/L Bone buffering of excess H + ions associated with release of Ca 2+ and Phos from bone Bone buffering of excess H + ions associated with release of Ca 2+ and Phos from bone Uremic acidosis increase skeletal muscle breakdown and diminish albumin synthesis  loss of lean muscle mass and fatigue Uremic acidosis increase skeletal muscle breakdown and diminish albumin synthesis  loss of lean muscle mass and fatigue Sodium bicarbonate or sodium citrate to keep HCO 3 above 22meq/L Sodium bicarbonate or sodium citrate to keep HCO 3 above 22meq/L

15. Secondary Hyperparathyroidism

16. Treatment of Secondary Hyperparathyroidism Phosphate binders: Phosphate binders: Low Phos diet (<800 mg/day) Low Phos diet (<800 mg/day) Ca based: Ca based: CaCO3 CaCO3 Ca acetate Ca acetate Non absorbable agent: Non absorbable agent: Sevelamer Hydrochloride (Renagel) Sevelamer Hydrochloride (Renagel) Sevelamer Carbonate (Renvela) Sevelamer Carbonate (Renvela) Lanthanum carbonate (Fosrenol) Lanthanum carbonate (Fosrenol) Aluminum binders. Aluminum binders. Vitamin D analogs: Vitamin D analogs: Calcitriol (Rocaltrol) Calcitriol (Rocaltrol) Paricalcitol (Zemplar) Paricalcitol (Zemplar) Doxercalciferol (Hectoral) Doxercalciferol (Hectoral) Calcimimetic: Cinacalcet (Sensipar) Calcimimetic: Cinacalcet (Sensipar)

17. Renal Osteodystrophy Types of Bone Disease Types of Bone Disease Osteitis fibrosa Osteitis fibrosa Osteomalacia Osteomalacia Adynamic bone disease Adynamic bone disease Target PTH Target PTH Stage 3 (GFR 30-59): 35-70 pg/mL Stage 3 (GFR 30-59): 35-70 pg/mL Stage 4 (GFR 15 to 29): 70-110 pg/mL Stage 4 (GFR 15 to 29): 70-110 pg/mL Stage 5 (GFR less than 15): 150-300 pg/mL Stage 5 (GFR less than 15): 150-300 pg/mL

18. Metastatic Calcification

19. Hypertension Mostly volume mediated Mostly volume mediated Start with ACEI/ARB and diuretic Start with ACEI/ARB and diuretic Thiazides become ineffective when GFR falls below 20 Thiazides become ineffective when GFR falls below 20 Goal is less than 130/80, but even lower systolic with urine prot/creat >1 Goal is less than 130/80, but even lower systolic with urine prot/creat >1

20. Anemia in CKD The primary cause of anemia in patients with CKD is insufficient production of erythropoietin (EPO) by the diseased kidneys. Other causes include: Iron deficiency. Secondary hyperparathyroidism. Decreased RBC lifespan. Folate deficiency.

21. K/DOQI Guidelines for Anemia in CKD Target Hgb between 11-12 g/dL Target Hgb between 11-12 g/dL Anemia work-up when Hgb <11g/dL (Hct is <33 percent) in pre- menopausal females and pre-pubertal patients. Hgb <12g/dL (Hct is <37 percent) in adult males and post-menopausal females. Use of erythropoietic agents (Epo,Procrit,Aranesp) Use of erythropoietic agents (Epo,Procrit,Aranesp)

22. Dyslipidemia Primary finding in CKD is hypertriglyceridemia Primary finding in CKD is hypertriglyceridemia Goal of LDL in CKD in similar to CHD – LDL <100, but there is not much evidence whether this is beneficial. Goal of LDL in CKD in similar to CHD – LDL <100, but there is not much evidence whether this is beneficial. One large study in CKD Stage V showed a negative association with very low cholesterol levels One large study in CKD Stage V showed a negative association with very low cholesterol levels

23. Preparation for Renal Replacement Therapy Refer to nephrology when GFR < 60 Refer to nephrology when GFR < 60 Early education of CKD Early education of CKD Choice of renal replacement therapy Choice of renal replacement therapy In-center hemodialysis In-center hemodialysis Peritoneal dialysis Peritoneal dialysis Home hemodialysis Home hemodialysis Access placement Access placement Referral to vascular surgery of AVF placement if patient choses HD and advising patient to save non-dominant arm from venopuctures and heplocks. Referral to vascular surgery of AVF placement if patient choses HD and advising patient to save non-dominant arm from venopuctures and heplocks.

24. What is Dialysis?

25. Initiation of Emergent Dialysis Uremic syndrome Uremic syndrome Refractory volume overload Refractory volume overload Uncontrollable hyperkalemia Uncontrollable hyperkalemia Severe metabolic acidosis Severe metabolic acidosis Steady worsening of renal function, with BUN exceeding 70-100 mg/dL or creatinine clearance of less than 15-20 ml/min/1.73 m2 Steady worsening of renal function, with BUN exceeding 70-100 mg/dL or creatinine clearance of less than 15-20 ml/min/1.73 m2

26. Diffusion Transport process by which a solute passively diffuses down its concentration gradient from one fluid compartment into the other Transport process by which a solute passively diffuses down its concentration gradient from one fluid compartment into the other

27. Dialysis Membrane

28. Contents of Dialysate Solution

29. Ultrafiltration (UF) Fluid removal occurs via hydrostatic pressure gradient across membrane generated by dialysis machine Fluid removal occurs via hydrostatic pressure gradient across membrane generated by dialysis machine

30. Peritoneal Dialysis (PD) Uses peritoneal membrane to transport solutes and water across two compartments Uses peritoneal membrane to transport solutes and water across two compartments One compartment is blood in the peritoneal capillaries, second compartment is dialysate solution in peritoneal cavity One compartment is blood in the peritoneal capillaries, second compartment is dialysate solution in peritoneal cavity

31. Continuous Renal Replacement Therapies (CRRTs)  Slower rate of solute or fluid removal per unit of time  Slower blood flow rate for the hemodynamically unstable patient Better tolerated than conventional therapy Better tolerated than conventional therapy

32. Complications Hypotension Hypotension Infection Infection Catheter Dysfunction Catheter Dysfunction

33. Hypotension Common Causes Common Causes Fluctuations in UF rate High UF rate Target dry weight set too low Dialysis solution too warm Food ingestion Autonomic neuropathy Antihypertensive medications

34. Hypotension-Cardiac Diastolic dysfunction due to LVH, ischemic heart disease Diastolic dysfunction due to LVH, ischemic heart disease Failure to increase cardiac rate Failure to increase cardiac rate Inability to increase cardiac output for other reasons Inability to increase cardiac output for other reasons

35. Hypotension Less common reasons Less common reasons Pericardial tamponade Pericardial tamponade Myocardial infarction Myocardial infarction Arrhythmia Arrhythmia Occult hemorrhage Occult hemorrhage Dialyzer reaction Dialyzer reaction Hemolysis Hemolysis Air embolism Air embolism

36. Dialysis Catheter Infections Localized exit site infection Localized exit site infection Erythema and/or crust, no purulent discharge, treat with antibiotics for up to 2 weeks Erythema and/or crust, no purulent discharge, treat with antibiotics for up to 2 weeks Tunnel Infection Tunnel Infection Purulent exudate present, and pain/warmth along the tunnel, removal of catheter with antibiotic administration for 3 weeks Purulent exudate present, and pain/warmth along the tunnel, removal of catheter with antibiotic administration for 3 weeks Systemic Infection Systemic Infection Fever, leukocytosis, may have no overt signs of catheter infection Fever, leukocytosis, may have no overt signs of catheter infection

37. Microbiology Staph species (40-81%) Staph species (40-81%) Enterococci, gram neg organisms, fungal organisms Enterococci, gram neg organisms, fungal organisms Empiric treatment with Vancomycin and Gentamicin Empiric treatment with Vancomycin and Gentamicin Treat with Nafcillin if MSSA! Treat with Nafcillin if MSSA!

38. Complications of Catheter Infection Endocarditis Endocarditis Osteomyelitis Osteomyelitis Thrombophlebitis Thrombophlebitis Spinal epidural abscess Spinal epidural abscess

39. Catheter Dysfunction Early Early less than 5 days less than 5 days Due to malposition or to intracatheter thrombosis Due to malposition or to intracatheter thrombosis Fibrin sleeves and mural thrombi Fibrin sleeves and mural thrombi Treatment Treatment Catheter exchange Catheter exchange TPA TPA

40. Catheter Dysfunction Late (more than 5 days) Late (more than 5 days) More likely due to intracatheter thrombosis than malposition More likely due to intracatheter thrombosis than malposition Treatment Treatment TPA TPA Catheter exchange Catheter exchange

41. Vascular Access Permanent catheter Permanent catheter AV graft AV graft AV fistula AV fistula

42. Permanent Catheter Cuffed venous catheters an alternative form of long-term access Cuffed venous catheters an alternative form of long-term access High rate of complications High rate of complications Thrombosis Thrombosis Infection Infection Inadequate blood flow Inadequate blood flow

43. AV Graft Advantages AV connection made using a tube graft from synthetic material AV connection made using a tube graft from synthetic material Maturation requires 2-3 weeks for adhesion of subcutaneous tunnel and graft Maturation requires 2-3 weeks for adhesion of subcutaneous tunnel and graftDisadvantages Higher rates of infection Higher rates of infection Higher rates of thrombosis Higher rates of thrombosis Shorter lifespan Shorter lifespan

44. AV fistula Advantages Subcutaneous anastomosis of artery to adjacent vein Subcutaneous anastomosis of artery to adjacent vein Safest longest lasting permanent access Safest longest lasting permanent access Excellent patency Excellent patency Lower morbidity Lower morbidity Lower complication Lower complicationDisadvantages Long maturation time Long maturation time Failure to mature in some patients Failure to mature in some patients May not be feasible in patients with vascular disease May not be feasible in patients with vascular disease