Chronic kidney disease, Hemodialysis

chronic kidney disease, diagnosis, management, prognosis, complications, renal replacement therapy, when to initiate hemodialysis, complication of hemodialysis, mortality and morbility.

1. CHRONIC KIDNEY DISEASE SHUMAYLA ASLAM, MD 2 ND YEAR RESIDENT EMILIO AGUINALDO COLLEGE MEDICAL CENTER- CAVITE DEPARTMENT OF INTERNAL MEDICINE [email protected]

2. Defined by the KDOQI CKD is defined as abnormalities of kidney structure or function, present for<3 months, with implications for health. Markers of kidney damage Albuminuria (AER >=30 mg/24 hours; ACR >=30 mg/g [>=3 mg/ mmol ]) Urine sediment abnormalities Electrolyte and other abnormalities due to tubular disorders Abnormalities detected by histology Structural abnormalities detected by imaging History of kidney transplantation GFR <60 mL /min/1.73 m2 for > 3 months [email protected]

3. ETIOLOGY 1. Glomerular diseases diabetes, autoimmune diseases, systemic infections, drugs, Neoplasia 2. Vascular diseases atherosclerosis, hypertension, ischemia, vasculitis , thrombotic microangiopathy ) 3. Tubulointerstitial diseases urinary tract infections, stones, obstruction, drug toxicity 4. Cystic disease polycystic kidney disease [email protected]

4. History of kidney transplantation. Chronic allograft nephropathy (non-specific findings of tubular atrophy, interstitial fibrosis, vascular and glomerular sclerosis) Rejection Drug toxicity ( calcineurin inhibitors eg : tacrolimus , cyclosporin ) BK virus nephropathy Recurrent disease (glomerular disease, oxalosis , Fabry disease) [email protected]

5. Leading Causes of CKD Diabetic nephropathy Glomerulonephritis Hypertension-associated CKD  (includes vascular and ischemic kidney disease and primary glomerular disease with associated hypertension) Autosomal  dominant polycystic kidney disease cystic and  tubulointerstitial  nephropathy [email protected]

6. Pathophysiology of CKD Two broad sets of mechanisms of damage: initiating mechanisms specific to the underlying etiology genetically determined abnormalities in kidney development or integrity, immune complex deposition and inflammation in certain types of glomerulonephritis , toxin exposure in certain diseases of the renal tubules and interstitium ) a set of progressive mechanisms, involving hyperfiltration and hypertrophy of the remaining viable nephrons, common consequence following long-term reduction of renal mass, irrespective of underlying etiology [email protected]

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8. Pathophysiology [email protected]

9. Staging of CKD In the absence of evidence of kidney damage, neither GFR category G1 nor G2 fulfill the criteria for CKD. [email protected]

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12. CLINICAL MANIFESTATION [email protected]

13. UREMIA the pathophysiology of the uremic syndrome can be divided into manifestations in three spheres of dysfunction: those consequent to the accumulation of toxins that normally undergo renal excretion, including products of protein metabolism; those consequent to the loss of other kidney functions, such as fluid and electrolyte homeostasis and hormone regulation; and progressive systemic inflammation and its vascular and nutritional consequences. [email protected]

14. UREMIA Hundreds of toxins that accumulate in renal failure have been implicated in the uremic syndrome. These include water-soluble, hydrophobic, protein-bound, charged, and uncharged compounds. Nitrogenous excretory products include guanidino compounds, urates and hippurates , products of nucleic acid metabolism, polyamines, myoinositol , phenols, benzoates, and indoles . [email protected]

15. A host of metabolic and endocrine functions is also impaired or suppressed, results in anemia , malnutrition, and abnormal metabolism of carbohydrates, fats, and proteins. plasma levels of many hormones, including PTH, FGF- 23, insulin, glucagon, steroid hormones including vitamin D and sex hormones, and prolactin , change with CKD as a result of reduced excretion, decreased degradation, or abnormal regulation. [email protected]

16. CKD is associated with worsening systemic inflammation. Elevated levels of C-reactive protein are detected along with other acute-phase reactants, decline with progressive reduction in GFR. Thus, the inflammation associated with CKD is important in the malnutrition-inflammation-atherosclerosis/calcification syndrome, which contributes in turn to the acceleration of vascular disease and comorbidity associated with advanced kidney disease. [email protected]

17. Fluid, Electrolyte, and Acid Base Disorders [email protected]

18. Potassium Homeostasis [email protected]

19. Metabolic Acidosis Earlier stages of CKD (stages 1–3) combination of hyperkalemia and hyperchloremic metabolic acidosis causes non-anion-gap metabolic acidosis. diabetic nephropathy or tubulointerstitial disease or obstructive uropathy Later stages of CKD (stage 4-5) anion-gap metabolic acidosis Mild: usually corrected with oral sodium bicarbonate supplementation. Modest: protein catabolism; [email protected]

20. Treatment: Hyponatremia responds to water restriction Salt restriction if with evidence of ECFV expansion Diuretics +/- metolazone in CKD III-V Kaliuretic diuretics for hyperkalemia Intractable hyperkalemia is an indication for dialysis Alkali supplementation when HCO 3 falls below 20-23 mmol /L [email protected]

21. Calcium and Phosphate Metabolism Bone manifestations High bone turnover with increased PTH levels: osteitis fibrosa cystica (classic lesion of secondary hyperparathyroidism) Low bone turnover with low or normal PTH levels: adynamic bone disease and osteomalacia [email protected]

22. Calcium and Phosphate Metabolism [email protected]

23. PTH considered a uremic toxin, and high levels are associated with muscle weakness, fibrosis of cardiac muscle, and nonspecific constitutional symptoms Clinical manifestations of severe hyperparathyroidism include bone pain and fragility, brown tumors, compression syndromes, and erythropoietin resistance [email protected]

24. Other Complications of Abnormal Mineral Metabolism Calciphylaxis ( calcific uremic arteriolopathy ) is a devastating condition exclusively in patients with advanced CKD patches of ischemic necrosis, especially on the legs, thighs, abdomen, and breasts vascular occlusion in association with extensive vascular and soft tissue calcification Warfarin treatment is considered a risk factor for calciphylaxis [email protected]

25. Treatment: Optimal management is prevention Low-phosphate diet Use of phosphate-binding agents calcium acetate and calcium carbonate side effects are calcium accumulation and hypercalcemia Sevelamer and lanthanum non-calcium-containing Calcitriol suppresses PTH secretion directly [email protected]

26. Cardiovascular Abnormalities leading cause of morbidity and mortality in CKD patients Ischemic Vascular Disease CKD is a major risk factor for ischemic CVD Heart Failure Abnormal cardiac function from myocardial ischemia, left ventricular hypertrophy and frank cardiomyopathy “low-pressure” pulmonary edema in advanced CKD Hypertension and Left Ventricular Hypertrophy Hypertension develops early in CKD Absence of hypertension may signify a salt-wasting form of CKD, effect of anti-HPN therapy, volume depletion or poor left ventricular function Use of EPO can also increase BP Pericardial Disease Chest pain with respiratory accentuation accompanied by friction rub Observed in advanced uremia ( underdialyzed , non-adherent patients) [email protected]

27. Treatment: In CKD + DM or proteinuria >1 g/day, BP goal is <130/80 with salt restriction as first-line therapy ACEi and ARBs may slow rate of decline of kidney function but can precipitate AKI and hyperkalemia Lifestyle changes Management of hyperlipidemia using dietary measures and statins Uremic pericarditis is an absolute indication for urgent initiation or intensification of dialysis (heparin-free) [email protected]

28. Hematologic Abnormalities Anemia Normocytic , normochromic anemia observed as early as CKD III and universal in CKD IV Causes include: Relative EPO deficiency Diminished RBC survival Bleeding diathesis Iron deficiency Hyperparathyroidism/marrow fibrosis Chronic inflammation Folate or vitamin B12 deficiency Hemoglobinopathy Co- morbids such as hypo/hyperthyroidism, pregnancy, HIV, autoimmune disease and immunosuppressive drugs Current practice is to target a hemoglobin concentration of 100–115 g/dl [email protected]

29. Abnormal hemostasis Prolonged bleeding time, decreased activity of platelet factor III, abnormal platelet aggregation and adhesion and impaired prothrombin consumption Greater susceptibility to thromboembolism especially if with nephrotic -range proteinuria [email protected]

30. Treatment: Recombinant human EPO should be initiated once there are adequate bone marrow iron stores Iron supplementation Blood transfusions increase the risk of hepatitis, iron overload, and transplant sensitization; they should be avoided unless the anemia fails to respond to ESA and the patient is symptomatic. Vitamin B12 and folate supplementation Desmopressin , cryoprecipitate, IV conjugated estrogen and EPO for abnormal bleeding time and coagulopathy Optimal dialysis corrects prolonged bleeding time [email protected]

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32. Neuromuscular Abnormalities CNS, Peripheral and Autonomic Neuropathy Early signs seen at CKD III Usually clinically evident at CKD IV Management: Most resolve with dialysis Successful renal transplantation may reverse residual neurologic changes [email protected]

33. Gastrointestinal and Nutritional Abnormalities Uremic Fetor: urine-like breath odor with dysgeusia (unpleasant metallic taste) Gastritis: peptic disease or mucosal ulcerations at any level of the GI tract Anorexia due to retention of uremic toxins Protein-Energy Malnutrition (PEM) [email protected]

34. Management: Protein restriction may slow the rate of renal decline at earlier stages Daily protein intake 0.60-0.75 g/kg/day with at least 50% provided by high-biologic value proteins 0.90 g/kg/day for CKD IV and those with PEM; daily total caloric intake of 35 kcal/kg Calcium and iron supplements may aggravate constipation and anorexia PEM: indication for renal replacement therapy [email protected]

35. Endocrine-Metabolic Disturbances Glucose metabolism Slowed response to glucose loading FBS normal or slightly elevated Diminished renal degradation of insulin Sexual dysfunction Low estrogen , menstrual abnormalities, inability to carry pregnancies to term Reduced plasma testosterone, oligospermia [email protected]

36. Management: Goals: FBS 90-130 mg/ dL , HbA1Z <7% Reduction in insulin and hypoglycemic agent doses Intensive dialysis and successful renal transplantation may reverse sexual dysfunction [email protected]

37. Dermatologic Abnormalities Pruritus , hyperpigmentation Nephrogenic fibrosing dermopathy : progressive subcutaneous induration especially on the arms and legs associated with exposure to gadolonium Treatment: Local moisturizers, mild topical steroids, UV radiation Minimizing exposure to gadolinium in CKD II and avoidance in CKD III to V Rapid removal of gadolinium by immediate dialysis for patients in whom MRI is highly necessary [email protected]

38. Diagnostics Renal Ultrasound Verifies presence of 2 kidneys, determines symmetry, estimates size and rules out masses/obstruction Finding : bilaterally small kidneys supports CKD (expect for early DM nephropathy, amyloidosis , HIV nephropathy, polycystic kidney disease) Renal Biopsy Not advised for bilaterally small kidneys Other contraindications: uncontrolled hypertension, active UTI, bleeding diathesis (including ongoing anticoagulation) and severe obesity Other Tests Perform specific tests to assess for specific target organ damage [email protected]

39. Management of progression and complications of CKD KDIGO 2012 Clinical Practise Guidelines for the evaluation and management of Chronic Kidney Disease [email protected]

40. PREVENTION OF CKD PROGRESSION BP and RAAS interruption We recommend that in both diabetic and non-diabetic adults with CKD and urine albumin excretion <30 mg/ 24 hours (or equivalent*) whose office BP is consistently >140mm Hg systolic or >90mm Hg diastolic be treated with BP-lowering drugs to maintain a BP that is consistently </= 140mm Hg systolic and </= 90mm Hg diastolic. [email protected]

41. We recommend that an ARB or ACE-I be used in both diabetic and non-diabetic adults with CKD and urine albumin excretion >300 mg/24 hours (or equivalent*). CKD and risk of AKI We recommend that all people with CKD are considered to be at increased risk of AKI. [email protected]

42. Protein intake We suggest lowering protein intake to 0.8 g/kg/day in adults with diabetes or without diabetes and GFR <30 ml/min/ 1.73 m 2 (GFR categories G4-G5), with appropriate education. We suggest avoiding high protein intake (>1.3 g/kg/day) in adults with CKD at risk of progression. [email protected]

43. Glycemic control We recommend a target hemoglobin A 1c (HbA 1c ) of ~7.0% (53 mmol /mol) to prevent or delay progression of the microvascular complications of diabetes, including diabetic kidney disease. (1A) We recommend not treating to an HbA 1c target of <7.0% (53 mmol /mol) in patients at risk of hypoglycemia . [email protected]

44. Salt intake We recommend lowering salt intake to <90mmol (<2 g) per day of sodium (corresponding to 5 g of sodium chloride) in adults, unless contraindicated. Lifestyle We recommend that people with CKD be encouraged to undertake physical activity compatible with cardiovascular health and tolerance (aiming for at least 30 minutes 5 times per week), achieve a healthy weight (BMI 20 to 25, according to country specific demographics), and stop smoking. [email protected]

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46. COMPLICATIONS ASSOCIATED WITH LOSS OF KIDNEY FUNCTION We recommend measuring serum levels of calcium, phosphate, PTH, and alkaline phosphatase activity at least once in adults with GFR <45 ml/min/1.73 m 2 (GFR categories G3b-G5) in order to determine baseline values and inform prediction equations if used. In people with GFR <45 ml/min/1.73 m2 (GFR categories G3b-G5), we suggest maintaining serum phosphate concentrations in the normal range according to local laboratory reference values. [email protected]

47. We suggest not to routinely prescribe vitamin D supplements or vitamin D analogs , in the absence of suspected or documented deficiency, to suppress elevated PTH concentrations in people with CKD not on dialysis. We suggest that in people with CKD and serum bicarbonate concentrations <22 mmol /l treatment with oral bicarbonate supplementation be given to maintain serum bicarbonate within the normal range, unless contraindicated [email protected]

48. Referral to specialists and models of care We recommend referral to specialist kidney care services for people with CKD in the following circumstances (1B): AKI or abrupt sustained fall in GFR; GFR <30 ml/min/1.73 m2 (GFR categories G4-G5)*; a consistent finding of significant albuminuria (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 (see Recommendation 2.1.3 for definition); urinary red cell casts, RBC >20 per high power field sustained and not readily explained; CKD and hypertension refractory to treatment with 4 or more antihypertensive agents; persistent abnormalities of serum potassium; recurrent or extensive nephrolithiasis ; hereditary kidney disease. [email protected]

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50. TIMING THE INITIATION OF RRT KDIGO 2012 Clinical Practise Guidelines for the evaluation and management of Chronic Kidney Disease [email protected]

51. We suggest that dialysis be initiated when one or more of the following are present: symptoms or signs attributable to kidney failure ( serositis , acid-base or electrolyte abnormalities, pruritus ); inability to control volume status or blood pressure; a progressive deterioration in nutritional status refractory to dietary intervention; cognitive impairment. This often but not invariably occurs in the GFR range between 5 and 10 ml/min/1.73 m2. (2B) [email protected]

52. Living donor preemptive renal transplantation in adults should be considered when the GFR is <20 ml/min/1.73 m2, and there is evidence of progressive and irreversible CKD over the preceding 6–12 months. [email protected]

53. Indication for dialysis initiation Absolute indications to start chronic dialysis include the following: Uremic pericarditis or pleuritis . Uremic encephalopathy [email protected]

54. Common indications   Declining nutritional status Persistent or difficult to treat volume overload Fatigue and malaise Mild cognitive impairment Refractory acidosis, hyperkalemia , and hyperphosphatemia [email protected]

55. "AEIOU"- "A"- intractable acidosis; "E"- electrolyte disarray ( K+, Na+, Ca++); "I" - intoxicants (methanol ethylene glycol, Li, ASA); "O"- intractable fluid overload; "U"- uremic symptoms (nausea, seizure, pericarditis,bleeding ). [email protected]

56. What's New [email protected]

57. Healthy Transitions Program for chronic kidney disease (October 2017) A randomized trial has shown that an outpatient care management program utilizing nurse care managers supported by a protocol-driven informatics system for patients with late-stage chronic kidney disease ( stage 4 to 5 CKD ) decreases hospitalization rates , increases the rate at which hemodialysis is begun without a hospitalization, decreases the use of catheters, and increases the selection of peritoneal dialysis . The informatics system provided daily reports for each patient that identified incomplete process steps (including discussions of renal replacement modality, dietary education, medication reconciliation, and home safety). Although the trial was small, these data suggest important benefits of such a program. [email protected]

58. Thank you [email protected]