Chronic Kidney Disease CKD Clinical Case

Chronic Kidney Disease Clinical presentation

1. Date and Time of Interview: March 01, 2019 6:00 PM GENERAL DATA Patient M.M., 73 years old, male, married, born on Feb 08, 1946, currently residing at Eastern Samar.

2. CHIEF COMPLAINT Dyspnea

3. HISTORY OF PRESENT ILLNESS 8 months prior to consult, patient had difficulty of breathing accompanied by easy fatigability characterized as getting tired easily of walking of approximately 10 steps. Patient claims to have loss of appetite and nausea. No other associated symptoms such as fever, chest pain, orthopnea, nor vomiting noted. Patient went in and out of the hospital but claims his condition won’t improve. He was advised to undergo dialysis but he refused to. Persistence of symptoms prompted consult.

4. PAST MEDICAL HISTORY Childhood Illnesses: No history of measles, chicken pox, rheumatic fever Adult Illnesses: DM for 10 years, with good compliance to medication: Metformin 50 mg/tab OD Hypertensive for 3 months, with good compliance to medication: Losartan 10 mg/tab OD No asthma

5. PAST MEDICAL HISTORY No allergies to any food/medications Previous Hospitalizations: Enlarged prostate gland, Borongan District Hospital, Jul 2018 Kidney disease, Tacloban Doctor’s Hospital, Dec 2018 Had 2 previous blood transfusions at Tacloban Doctor’s Hospital No previous surgical operations

6. FAMILY HISTORY DM (Paternal side) No family history of TB, heart disease, kidney disease, cancer, anemia, epilepsy, mental illnesses, hypertension, and asthma

7. PERSONAL AND SOCIAL HISTORY Patient is an alcoholic drinker and smoker 61 pack years

8. REVIEW OF SYSTEMS GENERAL: (+) Loss of appetite, no weight loss, no fever, no easy fatigability SKIN: (+) Pallor, no sores, no itchiness, no changes in hair and nails HEENT HEAD: No dizziness, no headache, no lightheadedness, no history of head injury EYES: (+) Blurring of vision, no redness, no pain, no excessive tearing, no spots, specks, or flashing lights seen EARS: Hearing intact, no tinnitus, no vertigo, no earache, no infection, no discharges NOSE AND SINUS: (+) Colds, no epistaxis, no nasal stuffiness, no itchiness MOUTH AND THROAT: No bleeding gums, no sore throat, no sore tongue, no dry mouth, no swallowing difficulty, no hoarseness of voice NECK: No pain, no stiffness BREAST: no palpable mass, no discharge, no skin changes, no breast enlargement RESPIRATORY: (+) Cough, (+) difficulty in breathing , no hemoptysis, no paroxysmal nocturnal, no chest pain

9. REVIEW OF SYSTEMS CARDIOVASCULAR: (+) Dyspnea, no palpitations, no orthopnea, no orthostatic hypotension GASTROINTESTINAL:, (+) Nausea, no vomiting, no constipation, no diarrhea, no pain in defecation URINARY: No urinary frequency, no dysuria, no polyuria, no nocturia , no urgency, no hematuria, no flank pain, no incontinence GENITALS: No pain or mass, no sores, no itchiness, no abnormal discharges PERIPHERAL VASCULAR: No pain and numbness, no intermittent claudication, no cramps, no varicose veins MUSCULOSKELETAL: No stiffness, no neck or low back pain NEUROLOGIC: No change in mood, attention or speech, seizures, numbness or loss of sensation, no tremors or other involuntary movement PSYCHIATRIC: No nervousness, no tension, no depression, no memory change, no suicide attempts HEMATOLOGIC: (+) Anemia, mo history of blood transfusion, no easy bruising, no bleeding tendency ENDOCRINE: No heat or cold intolerance, no excessive thirst or hunger, no excessive sweating  

10. PHYSICAL EXAMINATION General Survey: The patient was examined in a lying position, conscious, coherent, responsive, oriented to time, place, and person, in cardiorespiratory distress, with the following vital signs: BP= 180/100 mmHg HR= 86 bpm RR= 28 cpm T= 36.2 C

11. PHYSICAL EXAMINATION Skin: Senile complexion, with pallor, no jaundice, no cyanosis, dry, warm to touch, with good skin turgor, no lesions, no rashes, pinkish nail beds, smooth nails, with capillary refill of 3 seconds, no clubbing, no ridges, no breaks   Head: Skull is normocephalic , no dandruff, hair is black, short, evenly distributed with no signs of alopecia, no lesions, no lumps, no tenderness

12. PHYSICAL EXAMINATION Eyes: Pale palpebral and bulbar conjunctiva, anicteric sclerae pupils are 4 mm constricting to 2mm, equally round and reactive to light and accommodation, has direct and consensual light reflex, no excessive tearing, no lesions, no redness Ears: With good auditory acuity, no lesions, no discharges Nose: With pinkish nasal mucosa, nasal septum at midline, no obstruction, no discharges, no ulcers or polyps, no sinus tenderness, no nasal flaring

13. PHYSICAL EXAMINATION Mouth: Dry lips, pinkish and moist buccal mucosa, pinkish gingiva, no gum bleeding, symmetrical tongue protrusion, no sore tongue, tonsils not inflamed, uvula at midline   Neck: With neck vein engorgement, trachea at midline, thyroid gland moves with deglutition, no cervical lymphadenopathies, no bruits upon auscultation  

14. PHYSICAL EXAMINATION Throat: No palpable mass, no lumps, no lesions, no discharge Chest and Lungs: Symmetrical lung expansion, no lagging, no bulging, no intercostal and subcostal retractions; no masses, no tenderness; decreased breath sounds bibasal , dullness bibasal , decreased fremitus bibasal Cardiovascular: Adynamic precordium, no visible pulsations, no precordial bulging, no heaves, no thrills. PMI palpable at the 5th ICS MCL, regular rhythm, no murmurs

15. PHYSICAL EXAMINATION Abdomen: Globular, no ascites, no visible peristalsis, no engorged veins; no striae ; nontender , no masses, tympanitic in all quadrant, normoactive bowel sounds Extremities: (+) Bipedal pitting edema, no cyanosis, no atrophy, pulses full and equal

16. NEUROLOGIC EXAMINATION CN I: No anosmia CN II : Pupils 2-3mm in diameter, symmetrical, briskly reactive to light and good direct and consensual light stimulation. CN III, IV, VI: Full extraocular muscle movement. CN V: Facial sensation is intact to light touch. Corneal responses are intact. CN VII: Face is symmetric with normal eye closure and is able to smile.

17. NEUROLOGIC EXAMINATION CN VIII. (+) response to verbal stimuli CN IX and X: Palate elevates symmetrically. Phonation is normal. CN XI: Head turning and shoulder shrug are intact. CN XII: Tongue is midline with normal movements and no atrophy.

18. NEUROLOGIC EXAMINATION Patient can flex and extend both upper and lower extremities without limitation. Strength is full bilaterally. REFLEXES : Not examined There are no abnormal or extraneous movements. Patient able to walk with normal gait.

19. Course at er :

20. Course in the ward:

21. SALIENT FEATURES Patient is a 73 years old, male With a chief complaint of dyspnea History of present illness revealed difficulty of breathing, easy fatigability, loss of appetite, nausea PMH showed DM for 10 years, hypertension for 3 months Previous Hospitalizations: Enlarged prostate gland, Borongan District Hospital, Jul 2018 Kidney disease, Tacloban Doctor’s Hospital, Dec 2018

22. SALIENT FEATURES Upon PE: In cardiorespiratory distress with a BP= 180/100 mmHg Senile skin (dry), pallor Pale palpebral, dry lips Neck vein engorgement Dullness bibasal , decreased fremitus bibasal , decreased breath sounds bibasal Bipedal pitting edema

23. DIFFERENTIAL DIAGNOSIS

24. Congestive Heart Failure Shortness of breath Exertional dyspnea Easy fatigability Neck vein engorgement Bipedal edema × Rales × orthopnea × hepatomegaly -cannot totally rule out

25. Pleural Effusion Difficulty of breathing Cough Decreased breath sounds Decreased tactile fremitus Dullness on bibasal lung area -cannot totally rule out

26. CHRONIC GLOMERULONEPHRITIS RULE IN History of dyspnea, loss of appetite, nausea PMH hypertension PE pallor (anemia), neck vein distention, bilateral pitting edema RULE OUT No rales No pericardial friction rub No tenderness epigastric area No blood in the stool

27. CHRONIC KIDNEY DISEASE

28. Chronic Kidney Disease Encompasses a spectrum of different pathophysiologic processes associated with: abnormal kidney function progressive decline in glomerular filtration rate (GFR)

29. KDOQI : kidney damage for > 3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by either of the ff or GFR < 60 ml/min/1.73m2 for > 3 months with/without kidney damage Pathologic abnormalities Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests

30. Leading Categories of etiologies of CKD Diabetic nephropathy Glumerulonephritis Hypertension-associated CKD (vascular and ischemic kidney disease) Autosomal dominant polycystic kidney disease Other cystic and tubulointerstitial nephropathies

31. Classification of CKD

32. Chronic kidney disease The term applies to the process of continuing significant irreversible reduction in nephron number Typically corresponds to CKD stages 3-5.

33. End-stage disease Represents a stage of CKD where the accumulation of toxins, fluid and electrolytes normally excreted by the kidneys results in uremic syndrome This syndrome leads to death unless the toxins are removed by renal replacement therapy using dialysis or kidney transplantation

34. Pathophysiology of CKD Involves 2 broad sets of mechanisms of damage Initiating mechanisms specific to the underlying etiology Progressive mechanisms following long-term reduction in renal mass ( hyperfiltration and hypertrophy of the remaining viable nephrons ) irrespective of underlying etiology

35. Risk factors for CKD Childhood obesity Hypertension Diabetes mellitus Autoimmune disease Older age African ancestry Abnormal urinary sediment Family history of renal disease Previous episode of acute renal failure Presence of proteinuria Structural abnormalities of the urinary tract

36. Recommended equations for GFR computation 1. Equation from the modification of diet in renal disease study ESTIMATED GFR ( mL /min per 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.Cockroft – Gault Equation ESTIMATED CREATININE CLEARANCE ( mL /min) = (140-age x body weight, kg) 72 x P Cr (mg/ dL ) MULTIPLY BY 0.85 FOR WOMEN

37. Identification of at-risk population Normal annual mean decline in GFR with age is ~ 1mL/min per year per 1.73m 2 Peak GFR of ~120mL/min per 1.73m 2 is attained during the third decade of life At 70 y.o ., mean value of GFR is 70 mL /min per 1.73m 2 Mean GFR is lower in women than in men

38. Measurement of albuminuria Helpful for monitoring nephron injury and response to therapy in many forms of CKD especially chronic glomerular diseases 24-hour urine collection: gold standard Albumin-to- creatinine ratio in a spot first-morning urine: more practical

39. Chronic renal damage based on spot urine sample: Adult males: > 17 mg of albumin per gram of creatinine Adult females: 25 mg albumin per gram of creatinine Microalbuminuria Small excreted amounts, not detected by urinary dipstick or conventional tests for urine protein May be a marker for the presence of microvascular disease

40. Differences in clinical findings based on stage Usually not associated with any symptoms arising from reduced GFR Symptoms present are from the underlying disease (edema in nephrotic syndrome, hypertension in polycystic kidney disease, etc) Stages 1 and 2 CKD

41. Clinical and laboratory complications of CKD become more prominent with virtually all organs affected Most evident complications: Anemia and associated easy fatigability, decreasing appetite with progressive malnutrition Abnormalities in calcium, phosphorus and mineral-regulating hormones, such as 1,25(OH)2D3 ( calcitriol ) and parathyroid hormone (PTH) Abnormalities in sodium, potassium, water and acid-base homeostasis Stages 3 and 4 CKD

42. Stage 5 CKD Accumulation of toxins Results in marked disturbance in activities of daily living, well-being, nutritional status, and water and electrolyte homeostasis Uremic syndrome

43. Etiology and epidemiology Diabetic nephropathy: most frequent cause of CKD Hypertensive nephropathy: common cause of CKD in the elderly Progressive nephrosclerosis from vascular disease: renal correlate of atherosclerosis similar to CAD and CVD

44. Progressive nephrosclerosis Increasing incidence of CKD in elderly attributed partly to decreased mortality from the cardiac and cerebral complications of atherosclerotic vascular disease Vast majority of those with early stages of the renal disease will die from the cardiovascular and cerebrovascular consequences of vascular disease before they can progress to the most advanced stages of CKD

45. Early stage of CKD ( albuminuria , minor in GFR): now recognized as a major risk factor for CAD Factors determining inter-individual variability in rate of progression to CKD: heredity and sex Women with reproductive age : relatively protected against progression of many renal diseases (+) sex-specific responses to angiotensin II and its blockade

46. Pathophysiology and biochemistry of Uremia Plasma urea and creatinine concentrations There are hundreds of toxins that accumulate in renal failure: Water-soluble Hydrophobic Protein-bound Charged and uncharged compounds Middle molecules (500-1500Da mass of compounds)

47. Pathophysiology and biochemistry of Uremia Can be divided into manifestations in 3 spheres of dysfunction: 1. Due to accumulation of toxins normally undergoing renal excretion, including products of protein metabolism 2. Due to loss of other renal functions, such as fluid and electrolyte homeostasis and hormone regulation 3. Due to progressive systemic inflammation and its vascular and nutritional consequence

48. Uremic syndrome and the disease state associated with advanced renal impairment Involve more than just renal excretory failure Also involve impairment of numerous metabolic and endocrine functions normally undertaken by the kidneys Altered metabolism: anemia, malnutrition, abnormal metabolism of carbohydrates, fats and proteins Altered plasma levels of many hormones: PTH, insuln , glucagon, sex hormones and prolactin Worsening systemic inflammation: CRP and other acute phase reactants, levels of negative acute phase reactants ( albumin)

49. Evaluation and management of patients with CKD Initial approach History Physical examination

50. Clinical and Laboratory Manifestation Uremia leads to disturbances in the function of virtually every organ system

51. Fluid, electrolyte and acid-base disorders Sodium and water homeostasis Stable CKD: modest increase in total-body content of sodium and water In renal diseases, glomerulotubular balance is disrupted that dietary Na intake>urinary excretion Hyponatremia not common If with (+) ECF expansion – salt restriction

52. Diuretics: Thiazides : limited efficacy in stage 3-5 CKD Loop diuretics: useful in stages 3-5 CKD Dialysis: indicated for ongoing diuretic resistance with intractable edema and hypertension

53. Potassium homeostasis GFR decline is not necessarily accompanied by a parallel decline in urinary potassium excretion Hyperkalemia can be precipitated by: Increased dietary K intake, protein catabolism, hemolysis , hemorrhage, RBC transfusion, metabolic acidosis ACE inhibitors or ARBs, spironolactone , K-sparing diuretics

54. Certain CKD etiologies associated with earlier and more severe disruption of K- secretory mechanisms in the distal nephron Hyporeninemic hypoaldosteronism (DM) Obstructive uropathy Sickle cell nephropathy Hypokalemia is not common in CKD

55. Metabolic acidosis Common disturbance in advanced CKD Intact urine acidifying property BUT producing less ammonia unable to excrete normal quantity of H+ Concurrent hyperkalemia can further depress ammonia production

56. Advancing CKD Total urinary daily acid excretion limited to 30-40 mmol THUS anions of organic acids are retained Consequence: metabolic acidosis Most patients: mild metabolic acidosis, pH rarely <7.35, corrected with oral sodium bicarbonate

57. Disorders of calcium and phosphate metabolism Principal complications occur in the skeleton and the vascular bed, with occasional severe involvement of extraosseous soft tissues Bone manifestations of CKD 2 major manifestations: High bone turnover with inc. PTH ( osteitis fibrosa cystica = classic lesion of secondary hyperparathyroidism) Low bone turnover with dec . or normal PTH levels ( adynamic bone disease and osteomalacia )

58. High turnover bone disease from sec. hyperparathyroidism Mechanisms: Declining GFR leads to phosphate retention due to reduced excretion of phosphate Retained phosphate stimulates increased synthesis of PTH and growth of parathyroid gland mass Decreased levels of ionized calcium further stimulates PTH production

59. Mass of parathyroid glands increases progressively with CKD with the following patterns: Diffuse hyperplasia (polyclonal) Nodular growth (monoclonal) within diffuse hyperplasia Diffuse monoclonal hyperplasia (“adenoma” or tertiary autonomous hyperparathyroidism) Monoclonal (autonomous) hyperplasia predisposes to resistant hypercalcemia and may require surgical parathyroidectomy

60. Severe hyperparathyroidism Clinical Manifestations: Bone pain and fragility Brown tumors (bone cysts with hemorrhagic elements so that they appear brown in color) Rare compression syndromes Erythropoietin resistance PTH is also a uremic toxin: Muscle weakness Fibrosis of cardiac muscle Nonspecific constitutional symptoms

61. Hyperphosphatemia has a strong association with increased cardiovascular mortality in patients with stage 5 CKD Hyperphosphatemia + hypercalcemia = inc. vascular calcification Calciphylaxis Vascular occlusion in association with extensive vascular calcification Risk: warfarin use

62. Treatment of disorders of calcium and phosphate metabolism Secondary hyperparathyroidism and osteitis fibrosa : optimal management is prevention Low-phosphate diet, appropriate use of phosphate-binding agents Goal PTH level: between 150-300 pg/ mL (very low PTH levels associated with adynamic bone disease)

63. Cardiovascular abnormalities Cardiovascular disease: the leading cause of morbidity and mortality at every stage of CKD Any CKD stage is a major risk of ischemic vascular disease

64. Nontraditional Hypertension Hypervolemia Dyslipidemia Sympathetic overactivity Hyperhomocysteinemia Anemia Hyperphosphatemia Hyperparathyroidism Sleep apnea Generalized inflammation CKD-related Risk Factors for IHD

65. Heart failure May have frank pulmonary edema May either be systolic or diastolic dysfunction or both

66. Hypertension and left ventricular hypertrophy One of the most common complications of CKD developing early in the course of CKD Hypertension BP goal: < 130/80 mmHg CKD : compelling indication for initial use of ACEI or ARB Also lower intraglomerular pressure Determine baseline K level

67. If NO hypertension, Possibly due to: presence of a salt-wasting renal disease Effect of antihypertensive therapy Volume depletion May signify poor LV function

68. Treatment of cardiovascular abnormalities BP management Slow progression of kidney disease Prevent extrarenal complications of high BP (stroke, CV disease) Lifestyle changes Folate supplementation to hyperhomocysteinemia is of unproven benefit Hyperlipidemia Statins and other drugs: NO proven benefit for patients with advanced CKD DM and HPN: 2 most frequent causes of advanced CKD

69. Pericardial Disease Uremic pericarditis : diagnostic findings include pericardial pain with respiratory accentuation+friction rub ECG: PR-interval depression, diffuse ST-segment elevation Can be accompanied by pericardial effusion - - tamponade

70. Incidence reduced with prompt dialysis Treatment HD Pericardial d rainage

71. Hematologic abnormalities Normocytic , normochromic anemia As early as stage 3 CKD, universal by stage 4 Primarily due to insufficient production of erythropoietin by the diseased kidneys Others: iron deficiency, acute and chronic inflammation, folate and vitamin B12 deficiency, aluminum toxicity

72. Contributory comorbid conditions: Hypo/hyperthyroidism, pregnancy, HIV-associated disease, autoimmune disease, immunosuppressive drugs Anemia and exogenous EPO: poor prognosis indicators Blood transfusion is avoided unless anemia fails to respond to EPO and the patient is symptomatic Hb normalization: NOT beneficial to dialysis patients

73. Abnormal hemostasis Prolonged bleeding time Decreased platelet factor III activity Abnormal platelet aggregation and adhesiveness Impaired prothrombin consumption Treatment: Desmopressin , cryoprecipitate, IV conjugated estrogens, blood transfusions, EPO therapy Optimal dialysis will often correct a prolonged bleeding time

74. Neuromuscular abnormalities Due to retained nitrogenous metabolites and middle molecules including PTH Subtle clinical manifestations of uremic neuromuscular disease usually become evident at stage 3 CKD

75. Uremic neuromuscular disease Early: mild disturbances in memory and concentration, sleep disturbance Later: neuromuscular irritability, including hiccups, cramps, fasciculations or muscle twitching Peripheral neuropathy: after reaching stage 4 CKD Restless leg syndrome

76. Gastrointestinal and nutritional abnormalities Uremic fetor: urine-like odor on the breath from breakdown of urea to ammonia in saliva often with dysgeusia Anorexia, nausea and vomiting: due to retention of uremic toxins Protein-energy malnutrition: due to low protein and caloric intake

77. Endocrine-metabolic disturbances Impaired glucose metabolism : slow rate of post- prandial rise in response to a glucose load Metformin : contraindicated when the GFR is less than half of normal Men: dec . plasma testosterone levels; (+) sexual dysfunction and oligospermia Children: delayed or impaired sexual maturation even with dialysis

78. Dermatologic abnormalities Prevalent in progressive CKD Pallor from anemia Multiple ecchymoses from defective hemostasis Pruritus Hyperpigmentation is due to deposition of retained pigmented metabolites or urochromes Nephrogenic fibrosing dermopathy : progressive subcutaneous induration especially on the arms and legs

79. Management Rule out skin disorders Erythropoietin therapy Local moisturizers Mild topical glucocorticoids Oral antihistamines UV radiation

80. LABORATORY INVESTIGATIONS Serum creatinine levels, ABGs, CBC, U/A, Electrolytes, ECG Imaging studies RENAL ULTRASOUND-most useful Doppler sonography , nuclear medicine, CT or MRI studies

81. Renal biopsy Not advised if with bilaterally small kidneys Can usually be performed in early CKD (stages 1-3)

82. TREATMENT DIALYSIS Chronic dialysis can reduce incidence and severity of many of these disturbances so that overt and florid manifestations of uremia have largely disappeared in the modern health setting Even optimal dialysis therapy is not completely effective as renal replacement therapy, because some disturbances resulting from impaired renal function fail to respond to dialysis

83. Treatment Address hypertension aggressively Give diuretics if with volume overload Correct anemia 2000–6000 units subcutaneously once or twice weekly can increase Hb concentrations toward the normal range in most pts. Dietary protein restriction

84. Newer non-calcium-, non-aluminum-containing resins (e.g., sevelamer ) are also used. Hyperkalemia dietary potassium restriction Sodium polystyrene sulfonate ( Kayexalate )

85. Managing other complications of CKD AVOID Metformin, Meperidine, oral hypoglycemics that are eliminated by the kidney, NSAIDS

86. Thank you!