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Ckd 2016 100 1


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chronic kidney disease

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Ckd 2016 100 1

  1. 1. Chronic Kidney Disease: An Update (Part I) Yassin Ibrahim El-Shahat Consultant: Nephrology & Hypertension Chief Medical Officer Burjeel Hospital, Abu Dhabi
  2. 2. Objectives Upon completion of this talk the attendant will be able to:  Understand the pathophysiology of Chronic Kidney Disease  Recognize the signs and symptoms of Chronic Kidney Disease  Identify the disease progression and treatment interventions
  3. 3. Plan 1-What is the definition and Epidemiology of Chronic Kidney Disease (CKD)? 2-What is the Pathophysiology of CKD? 3-How should clinicians estimate the stage of CKD? 4-What laboratory tests and imaging should clinicians use to evaluate CKD? 5-What clinical manifestations should clinicians look for when evaluating patients for CKD? 6-How should clinicians construct a differential diagnosis of CKD? 7-When should clinicians consider consulting with a nephrologist for diagnosing patients with possible CKD? 8-How should Clinician Monitor CKD? 9-Which drugs and other agents cause acute kidney injury in patients with CKD?
  4. 4. Plan What is the definition and Epidemiology of Chronic Kidney Disease (CKD)?
  5. 5. What is the definition of CKD? Structural or functional abnormalities of the kidneys for >3 months, as manifested by either:  Kidney damage  Kidney damage can be either functional or structural  Functional abnormalities  Proteinuria, albuminuria  Abnormalities of urinary sediment (microscopic hematuria)  Structural abnormalities  On ultrasound scanning or other radiological tests (Polycystic kidney disease, reflux nephropathy, or other abnormalities)  The presence of GFR <60 mL/min/1.73 m2 for three months, with or without other signs of kidney damage as described above. Am J Kidney Dis 2012; 39:S1
  6. 6.  It is progressive tissue destruction with permanent loss of nephrons and renal function  CKD stage V: eGFR < 15 ml/min/1.73 m2  ESRD is a defined term that indicates advanced CKD which necessitates treatment by Renal Replacement Therapy-RRT (dialysis &/or kidney transplantation) What is the definition of CKD?
  7. 7. CKD as a Public Health Issue  Increases risk for all-cause mortality, CV mortality, End stage renal disease (ESRD), and other adverse outcomes. 1. NKF Fact Sheets. Accessed Nov 5, 2014. 2. USRDS. Accessed Nov 5, 2014. 3. Coresh et al. JAMA. 2007. 298:2038-2047.
  8. 8. 26 million Americans have CKD Coresh, et al., 2015 10.1 15.5 0.7 0 5 10 15 20 25 Persistent albuminuria with eGFR ≥ 60 (CKD Stage I-II) eGFR of 30-59 (CKD Stage III) eGFR of 15-29 (CKD Stage IV) Millionsofpeople 26 million American affected Prevalence is 11-13% of adult population in the US
  9. 9. Data Source: Special analyses, Medicare 5 percent sample. Known CKD stages presented as bars; curve showing “All codes” includes known CKD stages (codes 585.1-585.5) and the CKD-stage unspecified codes (585.9, and remaining non-585 CKD codes). Note: In previous years, this graph reported 585.9 codes as a component of the stacked bars. Abbreviation: CKD, chronic kidney disease. Trends in prevalence of recognized CKD, overall and by CKD stage, among Medicare patients aged 65+, 2000-2013 Stage I Stage II Stage III Stage IV Stage V Chronic Kidney Disease (CKD)
  10. 10. USRDS ADR, 2007 Prevalence of ESRD has been rising steadily
  11. 11. Prevalence of CKD by stage among NHANES participants, 1988-2012 Data Source: National Health and Nutrition Examination Survey (NHANES), 1988–1994, 1999-2004 & 2007–2012 participants aged 20 & older. Whisker lines indicate 95% confidence intervals. Abbreviations: CKD, chronic kidney disease.
  12. 12. Incident ESRD patients; rates adjusted for age & gender. Incidence varies widely by race and ethnicityRatepermillionpopulation Af Am N Am Hispanic Asian White Non-Hispanic USRDS ADR, 2007 Disproportionately affects African Americans and Hispanics
  13. 13. ESRD, end stage renal disease USRDS ADR, 2007 Diabetes and hypertension are leading causes of CKD Incident ESRD rates, by primary diagnosis, adjusted for age, gender, & race.
  14. 14. USRDS Incident counts & adjusted rates, by age USRDS ADR, 2007
  15. 15. Prevalence of Abnormalities at each level of GFR 0 10 20 30 40 50 60 70 80 90 15-29 30-59 60-89 90+ Estimated GFR (ml/min/1.73 m2 ) Proportionofpopulation(%) Hypertension* Hemoglobin < 12.0 g/dL Unable to walk 1/4 mile Serum albumin < 3.5 g/dL Serum calcium < 8.5 mg/dL Serum phosphorus > 4.5 mg/dL *>140/90 or antihypertensive medication p-trend < 0.001 for each abnormality
  16. 16. Prevalence of CKD by age & risk factor among NHANES participants, 1988-2012 Vol 1, CKD, Ch 1 16 Data Source: National Health and Nutrition Examination Survey (NHANES), 1988–1994, 1999-2004 & 2007–2012 participants aged 20 & older. Diabetes defined as either HbA1c >7%, self-reported, or currently taking glucose-lowering medications. Hypertension defined as BP ≥130/≥80 for those with diabetes or CKD, otherwise BP ≥140/≥90, or taking medication for hypertension. Abbreviations: BMI, body mass index; CKD, chronic kidney disease; CVD, cardiovascular disease; DM, diabetes mellitus; HbA1c, glycosylated hemoglobin; HTN, hypertension; SR, self-reported.
  17. 17. CKD is disproportionately costly Distribution of costs for CKD, HTN, & diabetic patients in Medicare population, 20014
  18. 18. Overall expenditures for CKD in the Medicare population age 65 & older Point prevalent Medicare CKD patients age 65 & older; costs are total expenditures per calendar year 28% of Medicare budget in 2013, up from 6.9% in 1993 ($42 billion in 2013) USRDS ADR, 2013
  19. 19. Data Source: Special analyses, Medicare 5 percent sample. Abbreviations: CKD, chronic kidney disease; CHF, congestive heart failure, DM, diabetes mellitus; PPPY, per person per year. Per person per year expenditures on Parts A, B, and D services for the CKD Medicare population aged 65+, by DM, CHF, and year, 1993-2013
  20. 20. Per person per month (PPPM) expenditures during the transition to ESRD, by dataset, 2011 Incident Medicare (age 67 & older) & Truven Health MarketScan (younger than 65) ESRD patients, initiating in 2008 USRDS ADR, 2013 Preventing progression of CKD will help hold down costs as the treatment of ESRD is expensive, requires some type of replacement therapy to maintain life.
  21. 21. Relationships between cardiac events and loss of life expectancy resulting from CVD by stage of CKD Marcello Tonelli et al. Circulation. 2016;133:518-536 The Lancet, Gansevoort et al; 2013, Elsevier.
  22. 22. Data source: Special analyses, Medicare 5 percent sample. January 1 of each reported year, point prevalent Medicare patients age 66 and older. Ref: 2012 patients. Abbreviation: CKD, chronic kidney disease. All-cause mortality rates (per 1,000 patient years at risk) for Medicare patients aged 66+, by CKD status and year, 2001-2013
  23. 23. Data source: Special analyses, Medicare 5 percent sample. January 1, 2013 point prevalent patients aged 66 and older. Adj: age/sex/race. Ref: all patients, 2013. Abbreviations: CKD, chronic kidney disease; CVD, cardiovascular disease; DM, diabetes mellitus. Adjusted all-cause mortality rates (per 1,000 patient years at risk) for Medicare patients aged 66+, by cardiovascular disease and diabetes mellitus, CKD status and stage, 2013
  24. 24. Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis 0.01 100 10 1 0.1 Annual mortality (%) 25–34 45–54 65–74 8535–44 55–64 75–84 Male Female Black White Dialysis General population Age (years) Am J Kidney Dis 2012; 39(S2): S1-246
  25. 25. Data Source: National Health and Nutrition Examination Survey (NHANES), 2001-2012 participants aged 20 & older. Abbreviations: CKD, chronic kidney disease. NHANES participants with CKD aware of their kidney disease, 2001-2012
  26. 26. Gaps in CKD Diagnosis In Diabetic Patients Szczech, Lynda A, et al. "Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes: The ADD-CKD Study (Awareness, Detection and Drug Therapy in Type-2 Diabetes and Chronic Kidney Disease)." PLOS One - In press (2014). 0 10 20 30 40 50 60 Not Appropriately Tested Appropriately tested - no diagnosis Appropriately tested - accurate diagnosis CKD Screening in Primary Care (% of patients) % of Patients
  27. 27. Improved Diagnosis of CKD In Diabetic Patients Studies demonstrate that clinician behavior changes when CKD diagnosis improves. Significant improvements realized in:1-3 • Increased urinary albumin testing • Increased appropriate use of ACEi or ARBs • Avoidance of NSAIDs prescribing among patients with low proteinuria &/or eGFR • Appropriate nephrology consultation 1. Wei L, et al. Kidney Int. 2013;84:174-178. 2. Chan M, et al. Am J Med. 2007:120;1063-1070. 3. Fink J, et al. Am J Kidney Dis. 2009,53:681-668.
  28. 28. Plan What is the Pathophysiology of CKD?
  29. 29. Pathophysiology of CKD
  30. 30. Risk Factors and Causes for CKD
  31. 31. Pathophysiology of CKD Stage I & II CKD Diminished Renal Reserve eGFR 50% eGFR Proteinuria Glomerulosclerosis Impaired/Sluggish Blood Flow Modifiable Factors -DM -Hypertension -Increase Protein & Fat intake -Smoking -Use of NSAIDS Non-Modifiable Factors -Heriditary -Age greater than 60 yrs old -Gender -Race Thickening &/or an in the amount of collagen in the basement membranes of the small vessels
  32. 32. Pathophysiology of CKD
  33. 33. Pathophysiological Events Underlying the Origin and Evolution of Hypertensive Nephropathy
  34. 34. Pathogenesis of kidney disease in patients with diabetes Muskiet, M. H. A. et al. (2013), Nat. Rev. Nephrol. doi:10.1038/nrneph.2013.272
  35. 35. Pathophysiology of CKD
  36. 36. Pathophysiology of CKD
  37. 37. Pathogenesis of disordered mineral metabolism in CKD Increase FGF-23 Hypocalcemia Increase PTH Bone Disease Severe inhibition of 1-α hydroxylase and 1,25 dihydroxyvitamin D Vit D Deficiency Vit D Resistance Hyperphosphatemia Decrease GFR
  38. 38. Pathogenesis of disordered mineral metabolism in CKD
  39. 39. Self-perpetuating triad formed by the interactions among anemia, chronic kidney disease (CKD) and congestive heart failure (CHF) that mutually potentiate each other and translate into mortality multipliers. Madhumathi Rao, Brian J.G. Pereira, Kidney International, Volume 68, Issue 4, 2005, 1432–1438 Optimal anemia management reduces CV morbidity, mortality, and costs in CKD
  40. 40. Madhumathi Rao, Brian J.G. Pereira, Kidney International, Volume 68, Issue 4, 2005, 1432–1438 Mechanisms of Anemia in CKD 􀂃 EPO deficiency 􀂃 Blood loss 􀂃 Shorter RBC life span 􀂃 Decreased bone marrow responsiveness to EPO 􀂃 Vitamin deficiencies 􀂃 Iron deficiency (poor iron absorption) 􀂃 High uremia level 􀂃 Intoxication impairing RBC development (Aluminium) 􀂃 Hemolysis (copper, chloramines) 􀂃 Chronic inflammation
  41. 41. Data Source: Special analyses, Medicare 5 percent sample. Patients aged 66 and older, alive, without end-stage renal disease, and residing in the U.S. on 12/31/2013 with fee-for-service coverage for the entire calendar year. Totals of patients for the study cohort: N=1,238,888; With CKD=132,840; Without CKD=1,106,048. Abbreviations: AFIB, atrial fibrillation; AMI, acute myocardial infarction; ASHD, atherosclerotic heart disease; CHF, congestive heart failure; CKD, chronic kidney disease; CVA/TIA, cerebrovascular accident/transient ischemic attack; CVD, cardiovascular disease; PAD, peripheral arterial disease; SCA/VA, sudden cardiac arrest and ventricular arrhythmias; VHD, valvular heart disease.. Cardiovascular disease in patients with or without CKD, 2013
  42. 42. Proposed feedback loops in cardiorenal syndrome (CRS) Marcello Tonelli et al. Circulation. 2016;133:518-536
  43. 43. Pathophysiology and definitions of the five subtypes of CRS Claudio Ronco et al. Eur Heart J 2010;31:703-711
  44. 44. Hyperlipidemia (Role ?)  Hyperlipidemia common in CRF- especially in Nephrotic Syndrome  Excessive lipids accelerate progression of renal disease  Cholesterol increases glomerular injury  Two known paths of hyperlipidemia progression in CRF:  Hyperlipidemia activates LDL receptors in mesangial cells  Increased synthesis of lipoproteins in the liver related to increased albumin production
  45. 45. Inflammation (Role ?)  Inflammatory response can be triggered by: tissue injury, infections, toxins, immune responses and/or Angiotensin II  Can be acute or chronic  Can affect the renal pelvis and interstitial tissue as in pyelonephritis  Can affect the glomeruli as in glomerulonephritis Legg, V.(2005). Complications of chronic kidney disease. AJN,105(6),40-50 CKD prolongs inflammatory reactions Causes of Inflammation in CRF  Infection  Anemia  Uremia – increases oxidation of proteins, lipids & carbohydrates, leading to vascular inflammation  Malnutrition – decreases antioxidants  Low serum albumin – decreases antioxidants
  46. 46. Inflammation- (Cont.)  Adverse effects of chronic inflammation  Decreased appetite  Muscle and fat wasting  Endothelial damage  Atherosclerosis  Hypoalbuminemia  Increased cardiovascular disease risk Legg, V.(2005). Complications of chronic kidney disease. AJN,105(6),40-50  Angio-II is an Inflammatory mediator causing: • Increased vascular permeability • Increased leukocyte infiltration (monocytes, macrophages) • Cell proliferation & hypertrophy
  47. 47. Genetic Considerations  Autosomal dominant Polycystic Kidney Disease  Alport’s hereditary nephritis  Familial FSGS  Nephronopthisis, Nephropathic Cystinosis (Fanconi’s Syndrome)  Medullary cystic kidney disease  Fabry’s disease Sanford, R. (2004). Autosomal dominant polycystic kidney disease. Retrieved February 8, 2006,
  48. 48. Polycystic Kidney Disease  Most Common Genetic Disorder  Numerous fluid-filled cysts in kidneys and renal tubules  Normal renal tissue replaced by cysts  Decreased function leads to ESRD Two Major Forms of PKD  Autosomal Dominant PKD (90%)  Occurs equally males and females, mainly Caucasians  One parent with ADPKD gene = 50% chance children will inherit disease  Gene mutation on chromosome 16 or 4  Autosomal Recessive PKD (10%)  1 in 4 babies (of parents with mutation)  Mutation on chromosome 6 Only treatment for both when arrived to ESRD = dialysis and kidney transplantation
  49. 49. Risk Factors for CKD Risk Factor Definition Examples Susceptibility factors Increase susceptibility to kidney damage Older age, Family H/O CKD, Reduction in kidney mass, Low Birthweight, Low income or education Initiation Factors Directly initiate kidney damage DM, HTN, Autoimmune Diseases, Systemic Infections, Urinary Stones, Lower UT Obstruction, Drug Toxicity Progression Factors Cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage Higher Level of Proteinuria, Higher BP, Poor Glycemic Control, Smoking ESRD Increase morbidity and mortality in kidney failure Lowe Dialysis Dose (KT/V), Temporary Vascular Access, Low Serum Albumin Level, Late Referal
  50. 50. Plan How should clinicians estimate the stage of CKD?
  51. 51. 2 simple tests will identify CKD in adults  eGFR - Estimated GFR from serum creatinine using a certain equation  UACR - Urine albumin to creatinine ratio on a “spot” urine sample  24-hour urine collections are NOT needed -Diabetics should be tested once a year. Others at risk can be tested less frequently as long as normal.
  52. 52. How should clinicians estimate GFR and the stage of CKD?  MDRD equation  GFR (mL/min per 1.73 m2)= 186.3 × (Scr mg/dL)−1.154 × age−0.203 × (1.210 if black) × (0.742 if female)  CKD-EPI equation GFR = 141 × minimum(Scr/κ, 1)α × maximum(Scr/κ, 1)-1.209 × 0.993Age × (1.018 if female) × (1.159 if black) Cockcroft-Gault Men: CrCl (mL/min) = (140 - age) x wt (kg) SCr x 0.81 Women: multiply by 0.85 Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males minimum indicates the minimum of Scr/κ or 1, maximum indicates the maximum of Scr/κ or 1
  53. 53. NICE Stages of CKD CKD Stage Description (eGFR ml/min/1.73m2) Stage 1 Normal eGFR (>90) With other evidence of kidney damage* Stage 2 eGFR 60 – 90 With other evidence of kidney damage* Stage 3a Stage 3b eGFR 45-59 eGFR 30-44 Stage 4 eGFR 15 – 29 Stage 5 eGFR < 15 * Evidence of chronic kidney damage includes: persistent microalbuminuria or proteinuria, haematuria, structural abnormalities, biopsy proven glomerulonephritis. K/DOQI CKD Classification
  54. 54. 24-yo Black Man 63-yo White Man 59-yo White Woman S. Cr 1.3 mg/dL 1.3 mg/dL 1.3 mg/dL GFR as estimated by CKD-EPI Study equation 66 mL/min/1.73 m2 45 mL/min/1.73 m2 55 mL/min/1.73 m2 The perils of using serum creatinine to “guess” level of renal function
  55. 55. Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-2012) Stage Description GFR (ml/min/1.73 m2) Prevalence* N (1000s) % 1 Kidney Damage with Normal or  GFR  90 5,900 3.3 2 Kidney Damage with Mild  GFR 60-89 5,300 3.0 3 Moderate  GFR 30-59 7,600 4.3 4 Severe  GFR 15-29 400 0.2 5 Kidney Failure < 15 or Dialysis 300 0.1 *Stages 1-4 from NHANES III (1988-2008). Population of 177 million with age 20. Stage 5 from USRDS (2012), includes approximately 230,000 patients treated by dialysis, and assuming 70,000 additional patients not on dialysis. GFR estimated from serum creatinine using MDRD Study equation based on age, gender, race and calibration for serum creatinine. For Stage 1 and 2, kidney damage estimated by spot albumin-to-creatinine ratio 17 mg/g in men or 25 mg/g in women in two measurements.
  56. 56. Classification of CKD Based on GFR and Albuminuria Categories: “Heat Map” Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppls. 2013;3:1-150.
  57. 57. Automatic eGFR by the laboratory reporting is best  GFR is the accepted measure of kidney function  GFR is difficult to infer from serum creatinine alone  Automatic reporting identifies CKD patients with apparently “normal” serum creatinine, reduces barrier to early detection, and identifies people at high risk for contrast agents and other nephrotoxins
  58. 58. Caveats to eGFR  An estimate based on population data, not the patient’s actual GFR  Not reliable when used with patients:  with rapidly changing creatinine levels (e.g., AKI in the ICU)  with extremes in muscle mass, e.g. cachexia or paraplegia
  59. 59. Plan What laboratory tests and imaging should clinicians use to evaluate CKD?
  60. 60. Evaluation for CKD  Blood  CBC with diff  Urea, Creatinine and Electrolytes with Ca2+ and phosphorous  PTH  HBA1c  LFTs  Uric acid  Fe2+ studies  Urine  Urinalysis with microscopy  Spot urine for microalbumin  24-urine collection for protein and creatinine (if needed)  Ultrasound -For hydronephrosis, cysts, and stones -To assess echogenicity, size, kidney symmetry
  61. 61.  If indicated by history or by findings:  Antinuclear antibody to evaluate for lupus and other autoimmune dis  Serologies for HBV, HCV, and HIV  Serum antineutrophil cytoplasmic antibodies for vasculitis  Serum and urine protein immunoelectrophoresis for multiple myeloma  Stages 4 and 5 CKD:  test for hyperkalemia, acidosis, hypocalcemia, hyperphosphatemia Evaluation for CKD (Cont.)
  62. 62. Urine albumin & protein to creatinine ratio  Albumin-to-creatinine ratio  Normal to mildly increased <30 mg/g  Moderately increased 30-300 mg/g  Severely increased >300 mg/g  Protein-to-creatinine ratio  Normal to mildly increased <150 mg/g  Moderately increased 150-500 mg/g  Severely increased >500 mg/g • Type 2 diabetes: screen for albuminuria regularly  Positive when >30 mg/g creatinine in a spot urine sample
  63. 63. Plan What clinical manifestations should clinicians look for when evaluating patients for CKD?
  64. 64. Chronic vs. Acute Renal Failure  Acute Renal Failure (ARF):  Abrupt onset  Potentially reversible  Chronic Renal Failure (CRF):  Progresses over at least 3 months  Permanent- non-reversible damage to nephrons
  65. 65. What clinical manifestations should clinicians look for when evaluating patients for CKD? • Recent diarrhea, bleeding, or dehydration may decrease renal perfusion that leads to acute kidney injury • A medication history may reveal a drug cause of CKD • History of HF or cirrhosis suggests decreased renal perfusion • Skin rash, arthritis, mononeuropathy, or systemic symptoms suggests vasculitis, including lupus • Findings associated with diabetes and hypertension • Infection with HBV, HCV, or HIV may cause proteinuria • Family history of kidney disease suggests polycystic disease, the Alport syndrome, or medullary cystic kidney disease
  66. 66. Signs & Symptoms Visual / Verbal Clues  Dry mouth, fatigue, nausea – d/t hyponatremia & uremia  Hypertension – d/t sodium & water retention  Hypervolemia – d/t sodium & water retention  Gray/yellow skin – d/t accumulated urine pigments  Cardiac irritability – d/t hyperkalemia  Muscle cramps – d/t hypocalcemia  Bone & muscle pain – d/t hypocalcemia/hyperphosphatemia  Restless leg syndrome – d/t toxins’ effects on the nervous system
  67. 67.  Check for orthostasis  Look for rashes and petechiae  Examine the fundus for diabetic retinopathy or hypertensive retinopathy  Evaluate for heart failure  A renal bruit suggests renal artery stenosis  Inflamed joints suggest vasculitis or autoimmune processes  Asterixis or encephalopathy suggests uremia Signs & Symptoms Visual / Verbal Clues
  68. 68. Manifestations of CKD
  69. 69. Stages and Clinical Features of Non-Diabetic CKD
  70. 70. Stages and Clinical Features of Diabetic CKD
  71. 71. Plan How should clinicians construct a differential diagnosis of CKD?
  72. 72. How should clinicians classify CKD and construct a differential diagnosis?  By GFR and albuminuria  Determine cause based on:  Presence or absence of systemic disease  Presumed location of damage in the kidney (glomerular, tubulointerstitial, vascular, or cystic)  Classify patients with CKD into 1 of 3 broad categories: Diabetic kidney disease Hypertensive kidney disease Non-hypertensive, non-diabetic kidney disease
  73. 73. Classification of CKD by Diagnosis  Diabetic Kidney Disease  Glomerular diseases (autoimmune diseases, systemic infections, drugs, neoplasia)  Vascular diseases (renal artery disease, hypertension, microangiopathy)  Tubulointerstitial diseases (urinary tract infection, stones, obstruction, drug toxicity)  Cystic diseases (polycystic kidney disease)  Diseases in the transplant (Allograft nephropathy, drug toxicity, recurrent diseases, transplant glomerulopathy)
  74. 74. Identify reversible causes  Think about volume contraction, urinary obstruction, or toxic effects of medications  Rx  ACEs/ARBs  NSAIDs  Aminoglycosides and amphotericin B  IV Radiocontrast agents
  75. 75. Plan When should clinicians consider consulting with a nephrologist for diagnosing patients with possible CKD?
  76. 76. Nephrology referral suggestions • Regardless of when you refer: • Obtaining preliminary evaluation (e.g. ultrasound, screening serologies) • Providing consultant with patient history including serial measures of renal function • To assist with diagnostic challenge (e.g. decision to biopsy) • To assist with therapeutic challenge (e.g. blood pressure or immunosuppression) • Preparation for renal replacement therapy, especially when GFR less than 30
  77. 77. *Significant albuminuria is defined as ACR ≥300 mg/g (≥30 mg/mmol) or AER ≥300 mg/24 hours, approximately equivalent to PCR ≥500 mg/g (≥50 mg/mmol) or PER ≥500 mg/24 hours **Progression of CKD is defined as one or more of the following: 1) A decline in GFR category accompanied by a 25% or greater drop in eGFR from baseline; and/or 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5ml/min/1.73m2/year. KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD Indications for Referral to Specialist Kidney Care Services for People with CKD • Acute kidney injury or abrupt sustained fall in GFR • GFR <30 ml/min/1.73m 2 (GFR categories G4-G5) • Persistent albuminuria (ACR > 300 mg/g)* • Atypical Progression of CKD ** • Urinary red cell casts, RBC more than 20 per HPF sustained and not readily explained • Hypertension refractory to treatment with 4 or more antihypertensive agents • Persistent abnormalities of serum potassium • Recurrent or extensive nephrolithiasis • Hereditary kidney disease • No clear etiology of CKD • Type 2 diabetes with proteinuria w/o coexistent retinopathy or neuropathy • Rapid decline in kidney function (>5 mL/min per 1.73 m2 per year)
  78. 78. Observational Studies of Early vs. Late Nephrology Consultation Chan M, et al. Am J Med. 2007;120:1063-1070. KDIGO CKD Work Group. Kidney Int Suppls. 2013;3:1-150. Variable Early Referral Mean (SD) Late Referral Mean (SD) P Value Overall Mortality % 11 (3) 23 (4) <0.00 01 1-Year Mortality % 13 (4) 29 (5) 0.028 Hospital Length of stay- day 13.5 (2.2) 25.3 (3.8) 0.000 7 Serum Albumin at start of Dialysis 3.62 (0.05) 3.40 (0.03) 0.001 Hematocrit at start of Dialysis 30.54 (0.18) 29.71 (0.10) 0.013
  79. 79. Plan How should Clinician Monitor CKD?
  80. 80. Monitoring of CKD  Serial measurements of  Creatinine  eGFR  Albumin  Protein-creatinine ratio in the 1st morning sample  Electrolytes including HCO3, Ca, Phosph, alkaline phosphatase, iron studies, intact PTH  Renal sonogram  Renal biopsy
  81. 81. Stage of CKD by eGFR and albuminuria categories
  82. 82. Clinical Practice Guidelines for the Detection, Evaluation and Management of CKD Stage Description GFR Evaluation Management At increased risk Test for CKD Risk factor management 1 Kidney damage with normal or  GFR >90 Diagnosis Comorbid conditions CVD and CVD risk factors Specific therapy, based on diagnosis Management of comorbid conditions Treatment of CVD and CVD risk factors 2 Kidney damage with mild  GFR 60-89 Rate of progression Slowing rate of loss of kidney function 1 3 Moderate  GFR 30-59 Complications Prevention and treatment of complications 4 Severe  GFR 15-29 Preparation for kidney replacement therapy Referral to Nephrologist 5 Kidney Failure <15 Kidney replacement therapy 1 Target blood pressure less than 130/80 mm Hg. Angiotension converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mg/g.
  83. 83. Plan Which drugs and other agents cause acute kidney injury in patients with CKD?
  84. 84. Medications and CKD  NSAIDS – inhibit prostaglandins decreasing GFR and reduced sodium excretion  Decongestants – elevate blood-pressure and increase renal damage  Antacids and laxatives containing magnesium & aluminum: causes mineral accumulation and metabolic complications  Herbal Remedies – (juniper berry, buckthorn bark, cascara bark, licorice root) can cause electrolyte imbalances which worsen with diuretic therapy  Aminoglycoside antibiotics,  Amphotericin B,  If Radiocontrast Agents essential: give  sodium bicarbonate or 0.9% normal saline IV before and after procedure for patients at increased risk for contrast nephropathy,  Consider N-acetylcysteine before and after radiocontrast only in high-risk patients  stop Metformin  Avoid high doses of Gadolinium Contrast in stages 4 and 5 due to risk for nephrogenic systemic fibrosis Campoy, S, Elwell, R.(2005). Pharmacology & CKD. AJN, 105(9),60-72.
  85. 85. Common Medications Requiring Dose Reduction in CKD  Allopurinol  Gabapentin  CKD 4- Max dose 300mg qd  CKD 5- Max dose 300mg qod  Reglan  Reduce 50% for eGFR< 40  Can cause irreversible EPS with chronic use  Narcotics  Methadone and fentanyl best for ESRD patients  Lowest risk of toxic metabolites • Renally cleared beta blockers o Atenolol, bisoprolol, nadolol • Digoxin • Some Statins o Lovastatin, pravastatin, simvastatin. Fluvastatin, rosuvastatin • Antimicrobials o Antifungals, aminoglycosides, Bactrim, Macrobid • Enoxaparin • Methotrexate • ColchicineAdjust dosing of other medications to avoid other AEs
  86. 86. Medications in CKD  CKD patients at high risk for drug-related adverse events  Several classes of drugs renally eliminated  Consider kidney function and current eGFR (not just SCr) when prescribing meds  Minimize pill burden as much as possible  Remind CKD patients to avoid NSAIDs  No Dual RAAS blockade (with exceptions)  Any med with >30% renal clearance probably needs dose adjustment for CKD  No bisphosphonates for eGFR <30  Avoid Gadolinium Contrast for eGFR <30
  87. 87. Clinical Bottom Line: Diagnosis... o CKD is defined as kidney damage or a GFR <60 mL/min per 1.73 m2 for > 3 months o Classify o Diabetic nephropathy o Hypertensive nephropathy o Nondiabetic, nonhypertensive kidney disease o Then, into groups based on levels of GFR and albuminuria o History and physical exam often point to a cause o Definitive diagnosis requires: o Diagnostic tests o Renal ultrasound o Sometimes renal biopsy o Identify risk factors o Know patient’s GFR using appropriate screening tools o Help your patient adjust medication o Modify diet o Partner and refer to specialist
  88. 88. Pathophysiology of CKD-CVD
  89. 89. Kidney damage and normal or  GFR Kidney damage and mild  GFR Severe  GFR Kidney failure Moderate  GFR Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 NephrologistPrimary Care Practitioner The Patient (always) and other subspecialists (as needed) GFR 90 60 30 15 Who Should be Involved in the Patient Safety Approach to CKD? Patient safety Consult?
  90. 90. Chronic Kidney Disease: An Update (Part II) Yassin Ibrahim El-Shahat Consultant: Nephrology & Hypertension Chief Medical Officer Burjeel Hospital, Abu Dhabi
  91. 91. Pathophysiology of CKD in DM Jun Wada, and Hirofumi Makino Clin. Sci. 2013;124:139-152