CKD by Dr Getachew (1).................pptx

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1. Chronic Kidney Disease Getachew Wondafrash (MD, Internist ,Nephrologist) 18-3-14EC 8/15/2024 1

2. My outline of presentation How we differentiate b/n AKI and CKD What are the different cause of normal or increased size of kidney in the presence of CKD What are the indication of RRT What are the different cause of CKD in our set up and in western set up 8/15/2024 2

3. CKD in Africa 8/15/2024 3 South Africa Hypertension – affects approximately 25% of the adult population Hypertension is the cause of 21% of end stage renal failure Diabetic nephropathy 15% 24% Zambia, 12.4% Egypt, 9% Sudan, 6% Ethiopia Naicker et al Clin Nephrol 2010, Ethn Dis 2009 Cameroon - referral patterns to nephrology Risk factors for CRF 61% hypertension, 26% DM 82% referred GFR<30ml/min Halle et al Re Fail 2009

4. CKD in Africa 8/15/2024 4 Nigeria – Causes of CRF Chronic GN 41% Hypertensive nephrosclerosis 26% Diabetes mellitus 13% Mean Cr Cl – 6.5ml/min, Av BP 170/106 Alebiosu et al African Health Sciences 2006 Nigeria- Audit of OPD -60% of patients had evidence of hypertensive end organ damage 18.2% CKD 18.2% Diabetic nephropathy Ayodele et al Cardiovasc J S Afr 2005

5. Why do we have an epidemic of diabetes?? 8/15/2024 5

6. So – a growing specialty driven by an “un-met need”, an epidemic of obesity and an aging population - Good News for Nephrologist but what does it mean for the patients? 8/15/2024 6

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8. Diabetic Nephropathy in Africa 8/15/2024 8 Diabetes – affects 9.4 million people in Africa Estimated prevalence of nephropathy in DM 6-24% Naicker et al Ethn Dis 2009 Prevalence of microalbuminuira - 43% (Ghana) Mean duration of DM development of microalbuminuria 10 years Eghan et al Ethn Dis 2007 ESRF is the Cause of Death in 30% of patients with type II DM in South Africa Diagnosis to proteinuria mean time 10 years Keeton et al Afr Med J 2004

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10. Ethiopia: Renal Diseases, CKD One report in the late 70’s indicated chronic glomerulonephritis to be the commonest cause of chronic renal failure.53% of 45 adults. Eth Med J1980; 18:37-44 Among patients with the Nephrotic Syndrome most had proliferative GN and there were a substantial number of patients with amyloidosis . Eth Med J 1982:20;125-130 Unpublished more recent data from Tikur Anbessa Hospital, the main teaching hospital of the AAU Medical School, indicate that diabetes and hypertension are the leading causes of CKD . Out of 150 consecutive patients with CKD, Diabetic nephropathy and hypertension accounted for 30% each. 8/15/2024 10

11. Ethiopia: Renal Services A renal unit was opened in the Tikur Anbessa Hospital, Addis Ababa, in 1980 with the assistance of a Cuban team from the Institute of Nephrology in Havana. The unit provides outpatient and inpatient services including dialysis (when available), is involved in under and postgraduate training of doctors and some research has also been done. The first peritoneal dialysis (PD ) was done in April 1980 and the first hemodialysis was done in June 1981. 8/15/2024 11

12. Ethiopia: Renal Services Acute PD was done with stylet catheters for hundreds of adult and pediatric patients with AKI over the years. Presently only HD is offered for AKI in the unit. The 1 st private dialysis unit opened in Addis Ababa in 2001. There are presently many private dialysis unit in ethiopia There are no patients on chronic PD in Ethiopia . 8/15/2024 12

13. Which of the following cause of CKD is not associated with normal or increased size of kidney? A -Diabetic nephropathy B- Amyloidosis C –Polycystic kidney disease D- HIV associated nephropathy (HIVAN) E- Chronic glomelronephritis 8/15/2024 13

14. Chronic Kidney Disease Definition and Classification (NKF-K/DOQI ) The presence of markers of kidney damage for 3 months, as defined by structural or functional abnormalities of the kidney with or without decreased GFR manifest by either pathological abnormalities or other markers of kidney damage, including abnormalities in the composition of blood or urine, or abnormalities in imaging tests . OR The presence of GFR <60mL/min/1.73 m2 for 3 months, with or without other signs of kidney damage as described above. 8/15/2024 14

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16. The term chronic renal failure(CRF) applies to the process of continuing significant irreversible reduction in nephron number and typically corresponds to CKD stages 3–5. The dispiriting term end-stage renal disease(ESRD) represents a stage of CKD where the accumulation of toxins, fluid, and electrolytes normally excreted by the kidneys results in the uremic syndrome . This syndrome leads to death unless the toxins are removed by renal replacement therapy , using dialysis or kidney transplantation. End-stage renal disease ---- stage 5 CKD . 8/15/2024 16

17. Pathophysiology of Chronic Kidney Disease The pathophysiology of CKD involves two broad sets of mechanisms of damage : (1) Initiating mechanisms (2) A set of progressive mechanisms , involving hyperfiltration and hypertrophy 8/15/2024 17

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19. Which of the following is not a risk factor CKD A_ Hypertension, diabetes mellitus B- Older age , African ancestry C- Family history of renal disease, D- A previous episode of acute kidney injury , and the presence of proteinuria E- Abnormal urinary sediment, or F- Structural abnormalities of the urinary tract. 8/15/2024 19

20. Identification of Risk Factors and Staging of CKD It is important to identify risk factors that increase the risk for CKD, even in individuals with normal GFR. Risk factors include hypertension, diabetes mellitus , autoimmune disease, older age , African ancestry, a family history of renal disease, a previous episode of acute kidney injury , and the presence of proteinuria , abnormal urinary sediment, or structural abnormalities of the urinary tract. 8/15/2024 20

21. In order to stage CKD , it is necessary to estimate the GFR . Two equations commonly used to estimate GFR are and incorporate the measured plasma creatinine concentration, age, sex, and ethnic origin . Many laboratories now report an estimated GFR, or " eGFR ," using one of these equations 8/15/2024 21

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23. Equations for Estimation of GFR 1. Equation from the MDRD study * eGFR (ml/min/1.73 m 2 ) = 1.86 x ( P Cr ) –1.154 x (age) –0. 203 Multiply by 0.742 for women Multiply by 1.21 for African Americans 2. Cockcroft - Gault equation Estimated Cr Cl (ml/min) = (140 – age) x body weight (kg) 72 x P Cr (mg/ dl ) Multiply by 0.85 for women 8/15/2024 23

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25. Stages 1 and 2 CKD are usually not associated with any symptoms arising from the decrement in GFR. 8/15/2024 25

26. If the decline in GFR progresses to stages 3 and 4, clinical and laboratory complications of CKD become more prominent . Virtually all organ systems are affected, but the most evident complications include anemia and associated easy fatigability ; decreasing appetite with progressive malnutrition 8/15/2024 26

27. .If the patient progresses to stage 5 CKD, toxins accumulate such that patients usually experience a marked disturbance in their activities of daily living, well-being, nutritional status, and water and electrolyte homeostasis, eventuating in the uremic syndrome . As noted, this state will culminate in death unless renal replacement therapy (dialysis or transplantation) is instituted 8/15/2024 27

28. Etiology and Epidemiology The relative contribution of each category varies among different geographic regions. The most frequent cause of CKD in North America and Europe is diabetic nephropathy , most often secondary to type 2 diabetes mellitus. 8/15/2024 28

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30. Pathophysiology and Biochemistry of Uremia 8/15/2024 30

31. It is thus evident that the serum concentrations of urea and creatinine should be viewed as being readily measured, but incomplete, surrogate markers for these compounds, and monitoring the levels of urea and creatinine in the patient with impaired kidney function represents a vast oversimplification of the uremic state 8/15/2024 31

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33. Fluid, Electrolyte, and Acid-Base Disorders 8/15/2024 33

34. Sodium and Water Homeostasis In most patients with stable CKD, the total-body content of sodium and water is modestly increased, although this may not be apparent on clinical examination. Leading to sodium retention and attendant extracellular fluid volume (ECFV) expansion. This expansion may contribute to hypertension , which itself can accelerate the nephron injury. As long as water intake does not exceed the capacity for water clearance, the ECFV expansion will be isotonic and the patient will have a normal plasma sodium concentration and effective osmolality 8/15/2024 34

35. . Hyponatremia is not commonly seen in CKD patients but, when present, can respond to water restriction. . If the patient has evidence of ECFV expansion ( peripheral edema, sometimes hypertension poorly responsive to therapy), he or she should be counseled regarding salt restriction. 8/15/2024 35

36. Resistance to loop diuretics in renal failure often mandates use of higher doses than those used in patients with near-normal kidney function. Ongoing diuretic resistance with intractable edema and hypertension in advanced CKD may serve as an indication to initiate dialysis 8/15/2024 36

37. Potassium Homeostasis In CKD, the decline in GFR is not necessarily accompanied by a parallel decline in urinary potassium excretion, which is predominantly mediated by aldosterone -dependent secretory events in distal nephron segments. Another defense against potassium retention in these patients is augmented potassium excretion in the GI tract . But subsequently thy will develop hyperkalemia 8/15/2024 37

38. Metabolic Acidosis Metabolic acidosis is a common disturbance in advanced CKD. Early non-anion-gap metabolic acidosis. Late -anion-gap metabolic acidosis 8/15/2024 38

39. Disorders of Calcium and Phosphate Metabolism The principal complications of abnormalities of calcium and phosphate metabolism in CKD occur in the skeleton and the vascular bed , 8/15/2024 39

40. Bone Manifestations of CKD The major disorders of bone disease can be classified into those associated with High bone turnover with increased PTH levels ( including osteitis fibrosa cystica, the classic lesion of secondary hyperparathyroidism) and Low bone turnover with low or normal PTH levels ( adynamic bone disease and osteomalacia ). Osteitis fibrosa cystica (OFC ) is  a skeletal disorder caused by an overproduction of parathyroid hormone from the overactive parathyroid glands . Osteitis fibrosa cystica is the late manifestation of the hyperparathyroidism. The incidence of bone lesions has decreased from 80% in the past to 15% in the present. 8/15/2024 40

41. Hyperparathyroidism stimulates bone turnover and leads to osteitis fibrosa cystica . 8/15/2024 41

42. Complications of adynamic bone disease include an increased incidence of fracture and bone pain and an association with increased vascular and cardiac calcification 8/15/2024 42

43. What do you think the leading cause of morbidity and mortality of patient with CKD? A- Cardiovascular disease B- Hyperkalemia C- Anemia D- Renal bone disease E- Uremic frost and uremic fetor F – All are the answer 8/15/2024 43

44. Cardiovascular Abnormalities Cardiovascular disease is the leading cause of morbidity and mortality in patients at every stage of CKD. The incremental risk of cardiovascular disease in those with CKD compared to the age- and sex-matched general population ranges from 10- to 200-fold , depending on the stage of CKD. 8/15/2024 44

45. Ischemic Vascular Disease The presence of any stage of CKD is a major risk factor for ischemic cardiovascular disease, including occlusive coronary , cerebrovascular , and peripheral vascular disease . The increased prevalence of vascular disease in CKD patients derives from both traditional ("classic") and nontraditional (CKD-related) risk factors. 8/15/2024 45

46. Heart Failure Abnormal cardiac function secondary to myocardial ischemia, left ventricular hypertrophy, and frank cardiomyopathy , in combination with the salt and water retention that can be seen with CKD, often results in heart failure or even episodes of pulmonary edema. Heart failure can be a consequence of diastolic or systolic dysfunction, or both. A form of "low-pressure" pulmonary edema can also occur in advanced CKD, manifesting as shortness of breath and a "bat wing" distribution of alveolar edema fluid on the chest x-ray. 8/15/2024 46

47. Hypertension and Left Ventricular Hypertrophy Hypertension is one of the most common complications of CKD. It usually develops early during the course of CKD and is associated with adverse outcomes, including the development of ventricular hypertrophy and a more rapid loss of renal function . . 8/15/2024 47

48. Pericardial Disease Chest pain with respiratory accentuation , accompanied by a friction rub, is diagnostic of pericarditis. Classic electrocardiographic abnormalities include PR-interval depression and diffuse ST-segment elevation . 8/15/2024 48

49. Which of the following is not true about anemia of CKD? A - normocytic normochromic anemia is observed as early as stage 3 CKD and is almost universal by stage 4. B-The primary cause in patients with CKD is insufficient production of erythropoietin (EPO) C-Additional factors include iron deficiency, anemia of chronic disease, severe hyperparathyroidism, and shortened red cell survival in the uremic environment. D -Co morbid conditions such as hemoglobinopathy can worsen the anemia E - None 8/15/2024 49

50. Hematologic Abnormalities Anemia A normocytic , normochromic anemia is observed as early as stage 3 CKD and is almost universal by stage 4. The primary cause in patients with CKD is insufficient production of erythropoietin (EPO) by the diseased kidneys. 8/15/2024 50

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52. Abnormal Hemostasis Patients with later stages of CKD may have a prolonged bleeding time, decreased activity of platelet factor III, abnormal platelet aggregation and adhesiveness, and impaired prothrombin consumption. Clinical manifestations include an increased tendency to bleeding and bruising, prolonged bleeding from surgical incisions, menorrhagia, and spontaneous GI bleeding. 8/15/2024 52

53. Neuromuscular Abnormalities Central nervous system (CNS), peripheral, and autonomic neuropathy as well as abnormalities in muscle structure and function are all well-recognized complications of CKD. 8/15/2024 53

54. Early manifestations of CNS complications include mild disturbances in memory and concentration and sleep disturbance . Neuromuscular irritability, including hiccups, cramps, and fasciculations or twitching of muscles, becomes evident at later stages . In advanced untreated kidney failure, asterixis , myoclonus , seizures, and coma can be seen 8/15/2024 54

55. Peripheral neuropathy usually becomes clinically evident after the patient reaches stage 4 CKD, Initially, sensory nerves are involved more than motor , lower extremities more than upper, and distal parts of the extremities more than proximal. Restless leg syndrome is a condition characterised by a nearly irresistible urge to move the legs , typically in the evenings. Restless legs syndrome typically occurs while sitting or lying down . It generally worsens with age and can disrupt sleep. The main symptom is a nearly irresistible urge to move the legs. Getting up and moving around helps the unpleasant feeling temporarily go away. Self-care steps, lifestyle changes or medication may help. 8/15/2024 55

56. Evidence of peripheral neuropathy without another cause (e.g., diabetes mellitus) is a firm indication for starting renal replacement therapy . 8/15/2024 56

57. Gastrointestinal and Nutritional Abnormalities Uremic fetor , a urine-like odor on the breath, derives from the breakdown of urea to ammonia in saliva and is often associated with an unpleasant metallic taste ( dysgeusia). Gastritis , peptic disease , and mucosal ulcerations at any level of the GI tract occur in uremic patients and can lead to abdominal pain, nausea, vomiting, and GI bleeding. These patients are also prone to constipation , which can be worsened by the administration of calcium and iron supplements . The retention of uremic toxins also leads to anorexia, nausea, and vomiting. 8/15/2024 57

58. Protein-energy malnutrition , a consequence of low protein and caloric intake , 8/15/2024 58

59. Endocrine-Metabolic Disturbances Glucose metabolism is impaired in CKD, as evidenced by a slowing of the rate at which blood glucose levels decline after a glucose load. 8/15/2024 59

60. . Dermatologic abnormalities ; Pallor due to anemia Echymosis , hematoma Pruritis , and excoriation (Ca++ deposits and secondary hyperparathyroidism) Yellowish discoloration of skin : urochromes Uremic frost : is seen in advanced uremia It is due to high concentration of urea in the sweat, and after evaporation of the sweat, a fine white powder can be found on the skin surface . 8/15/2024 60

61. Evaluation and Management of Patients with CKD 8/15/2024 61

62. Diagnostic approach Differentiate acute from CRF: the following findings characterize CRF Reduced kidney size on ultrasonography Long standing nocturia/frequent urinate at night and pruritus Finding of broad tubular casts or waxy casts on urine analysis Anaemia (not always) Renal osteodystrophy Duration >3 months Identification of aggravating factors (acute or chronic) Hypovolemia or hypotension Congestive heart failure Sepsis Nephrotoxins Malignant hypertension Obstructive uropathy Systemic lupus erythematosus 8/15/2024 62

63. Evidence of metabolic bone disease with hyperphosphatemia, hypocalcemia , and elevated PTH and bone alkaline phosphatase levels suggests chronicity . Normochromic, normocytic anemia suggests that the process has been ongoing for some time. The finding of bilaterally reduced kidney size (< 8.5 cm in all but the smallest adults) favors CKD. 8/15/2024 63

64. Cont … Other physical examination manifestations of CKD include edema and sensory polyneuropathy . The finding of asterixis or a pericardial friction rub not attributable to other causes usually signifies the presence of the uremic syndrome In addition, the evaluation of prostate size in men and potential pelvic masses in women should be undertaken by appropriate physical examination 8/15/2024 64

65. Laboratory Investigation Laboratory studies should Serum and urine protein electrophoresis, looking for multiple myeloma, should be obtained in all patients >35 years with unexplained CKD, especially if there is associated anemia and elevated, or even inappropriately normal, serum calcium concentration in the face of renal insufficiency. In the presence of glomerulonephritis, autoimmune diseases such as lupus and underlying infectious etiologies such as hepatitis B and C and HIV should be assessed. 8/15/2024 65

66. Serial measurements of renal function should be obtained to determine the pace of renal deterioration and ensure that the disease is truly chronic rather than acute or subacute and hence potentially reversible. Serum concentrations of calcium, phosphorus, vitamin D, and PTH should be measured to evaluate metabolic bone disease. Hemoglobin concentration, iron, B 12 , and folate should also be evaluated. A 24-h urine collection may be helpful, as protein excretion >300 mg may be an indication for therapy with ACE inhibitors or ARBs. 8/15/2024 66

67. Imaging Studies The most useful imaging study is a renal ultrasound, which can verify the presence of two kidneys, determine if they are symmetri c, provide an estimate of kidney size , and rule out renal masses and evidence of obstruction . 8/15/2024 67

68. If the kidney size is normal , it is possible that the renal disease is acute or subacute . The exceptions are diabetic nephropathy , amyloidosis , and HIV nephropathy , . Polycystic kidney disease 8/15/2024 68

69. Renal Biopsy In the patient with bilaterally small kidneys, renal biopsy is not advised 8/15/2024 69

70. Management of chronic renal failure The general management of the patient with chronic renal disease involves the following issues 1) Treatment of reversible causes of renal dysfunction 2) Preventing or slowing the progression of renal disease 3) Treatment of the complications of renal dysfunction 4) Identification and adequate preparation of the patient in whom renal replacement therapy will be required 8/15/2024 70

71. 1 . Treating reversible causes of renal dysfunction In addition to exacerbation of their original renal disease, patients with chronic renal disease, with a recent decrease in renal function may be suffering from an underlying reversible process such as : Hypotension or dehydration Administration of nephrotoxic drugs Urinary tract obstruction Sever hypertension Infection Correcting these reversible causes can improve the renal function 8/15/2024 71

72. 2. Treatment of the complications of renal dysfunction : a) Volume overload Dietary sodium restriction Diuretic therapy, usually with a loop diuretic given daily. b) Hyperkalemia: Low-potassium diet or concurrent use of a loop diuretic (to increase urinary potassium losses) often ameliorates the degree of hyperkalemia . Calcium gluconate ; 10 ml of 10% solution over 5 minutes Glucose plus insulin: Correction of acidosis : administration of bicarbonate Potassium exchange resins: Kayaxalate 8/15/2024 72

73. ……cont’d c) Metabolic acidosis : Alkali therapy is advocated to maintain the plasma bicarbonate concentration above 22 mEq /L. If alkali is given, sodium bicarbonate (in a daily dose of 0.5 to 1 mEq /kg per day) is the agent of choice. d) Hyperphosphatemia : Dietary phosphate restriction may limit the development of secondary hyperparathyroidism in patients with chronic renal failure. An intake of about 800 mg/day may be desirable but can be accomplished only by limiting protein intake 8/15/2024 73

74. ………….cont’d e) Hypertension: Salt restriction Diuretics: loop diuretics are recommended for the treatment of hypertension and edema in patients with chronic renal failure. Thiazide diuretics have additive effect when administered with a loop diuretic for refractory edema. Anti hypertensive drugs f) Anemia: Blood transfusion in selected patients Recombinant Erythropoietin may be given 8/15/2024 74

75. ………..cont’d g) Malnutrition: The desire to maintain adequate nutrition among patients with chronic renal failure clearly competes with attempts to slow the progression of renal dysfunction with the use of a low protein diet. 8/15/2024 75

76. Slowing the Progression of CKD There is variation in the rate of decline of GFR among patients with CKD. However, the following interventions should be considered in an effort to stabilize or slow the decline of renal function 8/15/2024 76

77. Goals of CKD management RETARD CKD PROGRESSION BP control RAS blockade & Proteinuria reduction Glycemic control Lipidemic control Smoking cessation Protein restriction Avoid nephrotoxic Adjustment of medication doses 8/15/2024 77

78. Smoking Vasoconstriction Thrombosis direct toxic effects Vascular endothelium Induces decline in renal function Increases in urine protein excretio n Smoking: Independent risk factor for progression of CKD 8/15/2024 78

79. Protein Restriction While protein restriction has been advocated to reduce symptoms associated with uremia, it may also slow the rate of renal decline at earlier stages of renal disease . 8/15/2024 79

80. Managing Other Complications of Chronic Kidney Disease Medication Dose Adjustment Some drugs that should be avoided include metformin , meperidine , and oral hypoglycemics that are eliminated by the kidney. NSAIDs should be avoided 8/15/2024 80

81. eGFR <30mL/min/1.73m2 Unexplained decline in kidney function (>15% drop in eGFR over 3 months) Proteinuria >1g/24hrs Glomerular hematuria (particularly if proteinuria present) CKD and hypertension that is hard to get to target Diabetes with eGFR <60mL/min/1.73m2 Unexplained anemia ( Hb <10 g/dl) with eGFR <60mL/min/1.73m2 Who should usually be referred to a Nephrologist? Appropriate referral is associated with 8/15/2024 81

82. Preparation for Renal Replacement Therapy Maintenance dialysis and kidney transplantation has extended the lives of hundreds of thousands of patients with CKD worldwide. 8/15/2024 82

83. Clear indications for initiation of renal replacement therapy for patients with CKD include Uremic pericarditis, Uremic encephalopathy Uremic bleeding, Intractable muscle cramping ,peripheral neuropathy, anorexia, and nausea not attributable to reversible causes such as peptic ulcer disease, Evidence of malnutrition , and Fluid and electrolyte abnormalities, principally hyperkalemia or ECF volume overload, that are refractory to other medical management 8/15/2024 83

84. Thank you 8/15/2024 84