CHRONIC KIDNEY DISEASE.pptx.............

Presentation of chronic kidney disease showing the aetiology, pathophysiology, risk factors and management. The presentation was prepared and presented by Moi University student together with their lecturer.

1. CHRONIC KIDNEY DISEASE Bonventure Machuka -MED IV Ronald Too –MED VI Facilitator: Prof. Owino Ong’or

2. Definition Progressive and irreversible loss of kidney function for ≥3 months as manifested by kidney damage with or without decreased GFR or GFR< 60ml/min/1.73 m ^2 with or without kidney damage. ESRD occurs when the GFR is <15ml/min/1.73m^2 and an individual cannot survive without renal replacement therapy. Death usually occurs due to electrolyte imbalances and accumulation of uremic toxins.

3. Anatomy of the kidney Kidneys are bilateral bean-shaped organs located in the retroperitoneum extending from T12 to L3 The right kidney is slightly lower due to the presence of the liver. Arterial supply ; renal arteries which are direct branches of the abdominal aorta. Venous drainage- right and left renal veins which empty to the inferior vena cava. Lymphatic - para-aortic lymph nodes located at the origin of the renal arteries . Nerve supply- Sympathetic from T10-L2 through the celiac and left aortic-renal ganglion and inferior hypogastric plexus -Parasympathetic from lt and rt vagus and inferior hypogastric plexus

4. Anatomy of the kidney

5. The Nephron It is the functional unit of the kidney A healthy adult has 1-1.5 million neurons

6. FUNCTIONS OF THE KIDNEY Through Excretion Remove metabolic waste products Remove excess fluid ; Regulate acid -base balance Regulate electrolyte levels Through Secretion Regulate blood pressure (renin secretion) Regulate red blood cell production (secretion of erythropoietin) Regulate calcium uptake (secretion of active Vitamin D)

7. Epidemiology 8.5%-9.8% globally Majority of the cases are stage 3 black> white More common in the elderly in whom those above 65 years of age have a stable disease as compared to patients below 30 years who have progressive disease. In Kenya, estimates show that about 4 million Kenyans have CKD with significant portion progressing to kidney failure.Out of this ,about 10,000 have ESRD and require dialysis yet only 10 % can access dialysis services.

8. Calculating GFR GFR={(140-age)×LBW(kg)×constant}/ serum creatinine(micro mol /l) Constant= 1.23 for men and 1.04 for women Normal GFR is 90-120 ml/min/1.73m²

9. Staging of CKD 1.Kidney Disease: Improving Global Outcome(KDIGO ) G1= eGFR >90 with underlying kidney disease G2= eGFR 60-89 considered mildly decreased function G3a= eGFR 45-59 mildly to moderately decreased kidney function G3b= eGFR 30-44 moderately to severely decreased kidney function G4= eGFR 15-29 severely decreased kidney function G5= eGFR <15 this is considered endstage Renal disease

10. Staging using Albuminuria A1=less than 30mg per day( normal to mildly increased albinuria) A2= 30-300mg per day( moderately increased) A3= >300mg( severely increased albuminuria)

11. In stage 1 and 2 ,GFR alone does not confirm diagnosis. Other markers of diagnosis must be present which include albuminuria. Urine sediment abnormalities, electrolyte and other abnormalities due to tubular disorders, histologic abnormalities, structural abnormalities detected by imaging or history of kidney transplant. Purpose of staging is to guide management including risk stratification for progression and complications of CKD

12. Risk factors Diabetes mellitus Hypertension Cardiovascular disease S moking Obesity Age and race Family history Nephrotoxins like NSAIDS and herbal medication Autoimmune disease like SLE

13. Etiology and Pathogenesis Any condition which destroys the normal structure & function of the kidney. Proportion of ESRF in brackets. Diabetic nephropathy(45%) Hypertension(25%) Glomerular diseases(10%) Interstitial diseases(5%) Systemic inflammatory diseases(5%) Polycystic kidney disease (2%)

14. Glomerular diseases that can lead to CKD Primary glomerular focal and segmental glomerulosclerosis (FSGS) , IgA nephropathy (Berger’s Disease) , membranous nephropathy rapidly progressive glomerulonephritis, Membranoproliferative Glomerulonephritis Type I and II (MPGN I and II) Secondary glomerular disease SLE, Amyloidosis, diabetic glomerulosclerosis , accelerated hypertension, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura , systemic sclerosis, sickle cell disease

15. Vascular disease Hypertensive nephrosclerosis . Renal artery stenosis Renal vein thrombosis Small and medium-sized vessel vasculitis Pulmonary -Renal Syndromes Goodpasture’s Syndrome (anti-basement membrane disease) Wegener’s Granulomatosis and other ANCA ( antineutrophil cytoplasmic antibody) associated diseases.

16. Prerenal causes This is due to decreased blood volume and renal perfusion. Examples include Heart failure-pump failure Haemorrhages GI ,cutaneous losses of fluid

17. Intrarenal HTN Renal artery disease Glomerulonephritis Diabetes mellitus Nephritic and nephrotic syndromes Adult polycystic kidney Infantile polycystic kidney disease Sjogren’s syndrome Sarcoidosis Artheroembolic disease

18. Postrenal Obstructive uropathy - BPH , Tumors , Kidney stones -Its worth noting that the Pre renal and Post renal causes lead to intrarenal causes . Other causes – Congenital PCKD

19. P athogenesis This involves two broad sets of mechanical damage; an initiating mechanism specific to the underlying etiology followed by a long term maladaptive mechanism. A normal kidney has innate ability to maintain GFR when injured as the remaining healthy nephrons undergo compensatory hypertrophy and hyperfiltration under the influence of vasoactive hormones, cytokines and growth factors. This allows normal clearance of the plasma solutes. Creatinine and urea levels only begin to rise after the GFR is reduced by 50%. Plasma creatinine doubles with 50% reduction in the GFR.

20. How does CKD develop? Common pathway Initial Pathologic Insult Reduced Nephron Mass Glomerular Injury Growth Promoters Acting on Intact Glomeruli End-Stage Kidney Glomerular Hypertrophy on intact Glomeruli

21. Pathophysiology cont … 1.Salt and Water Handling Abnormalities-  GFR Na+ and water retention = BP and edema 2.Hyperkalemia -  GFR K+ retention , Aldosterone  Na/K pump at DCT henceK 3. Hyperphosphatemia and Hypocalcemia -  calcitriol GI calcium absorption renal phosphate excretion 4. Metabolic Acidosis -  H+ excretion,  bone decalcification 5. Endocrine abnormalities- Secondary hyperparathyroidism- Low oestrogen levels (menstrual abnormalities-amenorrhea) Low testosterone levels –sexual dysfunction 6. Anaemia – decreased EPO secretion 7.Uremia – Urea retention

22. Management of Chronic Kidney Disease RONALD TOO

23. HISTORY Pay attention to the: Duration of symptoms – more than 3 months. Drug ingestion, including NSAIDS, analgesic and other medications such as herbal remedies. Previous medical and surgical history, e.g. previous chemotherapy, multi systemic diseases such as SLE , DM ,HPTN . Previous occasions on which urinalysis or measurement of urea and creatinine might have been performed and the results. Family history of renal disease eg PCKD

24. SYMPTOMS The early stages of CKD are often completely asymptomatic. Symptoms are common when the serum urea concentration exceeds 40mmol/L , but many patients develop uraemic symptoms at lower levels of serum urea. Symptoms include: General body malaise Loss of appetite Insomnia Nocturia and polyuria due to impaired concentrating ability Itching

25. SYMPTOMS Nausea , vomiting and diarrhoea Paraesthesia due to polyneuropathy Bone pain due to metabolic bone disease Paraesthesia and tetany due to hypocalcaemia Symptoms due to salt and water retention - peripheral or pulmonary edema Symptoms due to anemia – easy fatigability, palpitations Amenorrhoea in women; erectile dysfunction in men.

26. Uremic Syndrome Organ System Symptoms Signs General Fatigue, weakness, hypothermia Sallow-appearing, chronically ill, pallor Skin Uremic frost, pruritus , easy bruisability , Pallor, ecchymoses, excoriations, edema, xerosis ENT Metallic taste in mouth, epistaxis Urinous breath Eye Pale conjunctiva CVS Pericarditis, atherosclerosis, HTN, hyperlipidemia, volume overload, CHF, cardiomyopathy, Dyspnea on exertion, retrosternal pain on inspiration Hypertension, cardiomegaly, friction rub

27. Organ System Symptoms Signs Gastrointestinal Anorexia, nausea, vomiting, Hiccups, GI bleeding Genitourinary Nocturia, erectile dysfunction, amenorrhoea Isosthenuria (urine w. s.g . nearly = plasma) Neuromuscular Restless legs, numbness and cramps in legs Metabolic Hyperkalemia, hyperPO4, acidosis, low Ca, high PTH, Neurologic Generalized irritability and inability to concentrate, decreased libido, sleep disturbances, headache, seizures, encephalopathy, coma Stupor, asterixis , myoclonus, peripheral neuropathy Hematologic Anemia, bleeding Pallor, ecchymosis

28. PHYSICAL EXAMINATION BP measurement; HTN often occurs in CKD due to underlying renal pathology or hypervolemia due to impaired water excretion Pallor as an indication of anemia should be assessed for by examining sites where capillary beds are visible through the mucosa (e.g., conjunctiva, palm, and nail beds ) Assessment for any sign of hypervolemia by noting the presence/absence of edema, rales, hepatic enlargement/tenderness, or cardiac gallop.

29. PHYSICAL EXAMINATION Cardiac auscultation to detect a pericardial rub due to pericarditis or diminished heart sounds secondary to a pericardial effusion. Rectal and vaginal examination may disclose evidence of an underlying cause of renal failure, particularly urinary obstruction, and should always be performed.

30. INVESTIGATIONS a) Urinalysis Haematuria may indicate glomerulonephritis, but other sources must be excluded. Proteinuria , if heavy, is strongly suggestive of glomerular disease. Urinary infection may also cause proteinuria. Glycosuria – DM but normal blood glucose is common in CRF.

31. INVESTIGATIONS b) Urine microscopy WBCs indicate active bacterial urinary infection. Sterile pyuria suggests papillary necrosis or renal tuberculosis. Eosinophils-allergic tubule-interstitial nephritis/cholesterol embolization. Granular casts are formed indicate active renal disease. RBC casts -glomerulonephritis . Red cells – cause anywhere between the glomerulus and the urethral meatus.

32. INVESTIGATIONS c) Urine biochemistry 24-hour creatinine clearance is useful in assessing the severity of renal failure. Urine osmolality is a measure of concentrating ability. Early-morning urine samples should be cultured if tuberculosis is suspected.

33. INVESTIGATIONS d) Serum biochemistry UECs - Urea and creatinine, K+, po4- elevated, low bicarbonate, Ca+, Na+ LFTs may show low albumin Electrophoresis and immunofixation - suspected myeloma . Rhabdomyolysis- Extreme elevations of creatine kinase and a disproportionate elevation in serum creatinine and potassium compared to urea.

34. INVESTIGATIONS e) CBC – Anaemia (normocytic normochromic) Eosinophilia:vasculitis , allergic tubulointerstitial nephritis, or cholesterol embolism. f)ESR - Markedly raised ESR suggests myeloma or vasculitis. g) BS for mps - Malaria is a major cause of glomerular disease in the tropics

35. INVESTIGATIONS I) Immunology Autoantibody screening is useful in detection of SLE, scleroderma , Wegener's granulomatosis and microscopic polyangiitis , and Goodpasture's syndrome . ASOT & anti-DNase B: post-streptococcal glomerulonephritis. Antibodies to hepatitis B and C: membranous nephropathy (hepatitis B) or to cryoglobulinaemia renal disease (hepatitis C). Antibodies to HIV raise the possibility of HIV-associated renal disease.

36. RADIOLOGICAL IX Ultrasound . Every patient should undergo ultrasonography (for renal size and to exclude hydronephrosis ) Plain abdominal radiography and CT (without contrast) to exclude renal stones or nephrocalcinosis. Intravenous urography is seldom necessary in advanced renal disease. CT is also useful for the diagnosis of retroperitoneal fibrosis and some other causes of urinary obstruction, and may also demonstrate cortical scarring. MRI . Magnetic resonance angiography in renovascular disease.

37. Renal biopsy This should be performed in every patient with unexplained renal failure and normal-sized kidneys, unless there are strong contraindications.

38. TREATMENT The goals of treatment include: Preventing or slowing the progression of renal disease Treatment of the complications of renal dysfunction Identification and adequate preparation of the patient in whom renal replacement therapy will be required

39. a) SLOWING THE PROGRESSION OF RENAL DISEASE Treat the underlying condition- E.g. obstruction, infection, HPTN, DM renal artery stenosis Aggressive BP control to target value: 130/80 in CKD alone and 125/75 if diabetic and Proteinuria > 1g/day – ACE inhibitors and ARBs ACE inhibitors may be acceptable in many patients with creatinine >3.0mg/ dL Caution with use of ACE inhibitors in renal artery stenosis Aggressive glycemic control in diabetes mellitus: Target HbA1C <7 %. Avoid nephrotoxins eg IV contrast, NSAIDS, Aminoglycosides

40. a) SLOWING THE PROGRESSION OF RENAL DISEASE Treat hyperlipidemia with HMG-COA reductase inhibitors to slow development of vascular disease Treat infections Dietary restrictions: Sodium 1-4g/day Potassium 3.5g/day avoid bananas Protein (0.6/kg) 60g of protein with adequate calories

41. b) TREATMENT OF COMPLICATIONS OF RENAL DYSFUNCTION 1. Anaemia Erythropoietin: 80-120U/kg weekly or Darbepoietin Iron supplements in patients with reduced iron stores. 200mg elemental Ferrous sulfate iron PO daily. Targets- Hb 10-12mg/dl, ferritin >100ug/l transferrin saturation >20%

42. b) TREATMENT OF COMPLICATIONS OF RENAL DYSFUNCTION 2. Hyperphospatemia Dietary restrictions (milk, eggs, cheese) Phosphate binders eg . Calcium carbonate up to 3g/day, Aluminium hydroxide begin 1g/day increase as required ) 3.Hypocalcemia Calcium supplements +/- calcitriol

43. b) TREATMENT OF COMPLICATIONS OF RENAL DYSFUNCTION 4. Hyperparathyroidism Calcitriol or vitamin D analogues 5. Volume overload Diuretics or ultra filtration 6. Uremic bleeding Desmopressin 0.3ug/kg IV OR 3ug/kg intranasally

44. b) TREATMENT OF COMPLICATIONS OF RENAL DYSFUNCTION 7. Hyperkalemia Potassium restriction and a void drugs that raise potassium e.g. NSAIDS In severe hyperkalemia Calcium gluconate – stabilizes cardiac muscles Shift potassium into cells using insulin – add dextrose Bicarbonate – esp if academic Beta2 agonists - albuterol Potassium-binding resins – kayexylate Diuretics – furosemide Hemodialysis Monitor ECG changes

45. b) TREATMENT OF COMPLICATIONS OF RENAL DYSFUNCTION 8. Metabolic acidosis Sodium bicarbonate 1g tds increase as required; Goal HCO3 > 22mmol/l Alkali therapy to maintain serum bicarbonate above 22mmol/l. Sodium bicarbonate is the alkali of choice (0.5-1meq/kg/day). Sodium citrate Dialysis 9. Immunosuppression: Identify and treat infections early 10. Malnutrition: Nutritional support

46. b) TREATMENT OF COMPLICATIONS OF RENAL DYSFUNCTION 11. Infection and vaccination CKD increase risk for infection (bacterial-pulmonary and genitourinary)-worsens with the decline in kidney function Preventive measures include influenza and pneumococcal immunization. Adults with all stages of CKD should be offered annual vaccination with influenza virus unless contraindicated. Adults with stage 4 and 5 CKD at high risk of progression: hepatitis B. Adults with stages 4 and 5 should be vaccinated with polyvalent pneumococcal vaccine unless contraindicated. Patients who have received pneumococcal vaccination should be offered revaccination within five years.

47. b) TREATMENT OF COMPLICATIONS OF RENAL DYSFUNCTION OTHER PROBLEMS Restless leg : Clonazepam Peptic ulcers : PPI/Histamine2 Receptor antagonists Sensory neuropathy : Amitriptyline, gabapentine Depression : supportive therapy

48. RENAL REPLACEMENT THERAPY

49. Introduction The aim is to mimic the excretory functions of the normal kidney, including excretion of nitrogenous wastes, maintenance of normal electrolyte concentrations, and maintenance of a normal extracellular volume . However, it does not replace the endocrine and metabolic functions of the kidney. Treatment modalities include: Hemodialysis Peritoneal dialysis Transplantation

50. Criteria for initiating patients on maintenance dialysis include: Pericarditis or pleuritis (urgent indication ). Progressive uremic encephalopathy or neuropathy, with confusion , asterixis , myoclonus, wrist or foot drop, or, in severe, cases, seizures (urgent indication ). A clinically significant bleeding diathesis attributable to uremia. Fluid overload refractory to diuretics. Hypertension poorly responsive to antihypertensive medications. Persistent metabolic disturbances that are refractory to medical therapy. Persistent nausea and vomiting. Evidence of malnutrition.

51. Indications for dialysis

52. Hemodialysis

53. HEMODIALYSIS Blood is run through a semi-permeable filter membrane bathed in dialysate Composition of the dialysate is altered to adjust electrolyte parameters Electrolytes and some toxins pass through filter By controlling flow rates (pressures), patient's intravascular volume can be reduced Most chronic hemodialysis patients receive 3 hours dialysis 3 days per week

54. Complications Of Hemodialysis Problem Clinical Features Cause Treatment Hypotension during dialysis Sudden ↓BP; often leg cramps; sometimes chest pain Fluid removal and hypovolemia Saline infusion; exclude myocardial infarction; quinine may help cramp Cardiac arrhythmias ↓BP; sometimes chest pain Potassium and acid-base shifts Check K + and arterial blood gases; review dialysis prescription; ? stop dialysis Haemorrhage Blood loss (overt or occult), ↓BP Anticoagulation, vascular access Stop dialysis; seek source; consider heparin-free treatment

55. Problem Clinical Features Cause Treatment Air embolism Circulatory collapse, cardiac arrest Disconnected or faulty lines and equipment malfunction Stop dialysis Dialyser hypersensitivity Acute circulatory collapse Allergic reaction to dialysis membrane or sterilisant Stop dialysis; change to different artificial kidney Emergencies between treatments Pulmonary edema Systemic sepsis Breathlessness Rigors, fever, ↓BP Fluid overload Usually involves vascular access devices (catheter or fistula) Ultrafiltration ± dialysis Blood cultures, antibiotics

56. Peritoneal Dialysis Involves insertion of a permanent Silastic catheter into the peritoneal cavity. Two liters of sterile, isotonic dialysis fluid are introduced and left in place for approximately 6 hours. During this time, metabolic waste products diffuse from peritoneal capillaries into the dialysis fluid down a concentration gradient. The fluid is then drained and fresh dialysis fluid introduced. The inflow fluid is rendered hyperosmolar by the addition of glucose; this results in net removal of fluid from the patient on each cycle (ultrafiltration).

57. PERITONEAL DIALYSIS

58. Abdominal cavity is lined by peritoneal membrane which acts as a semi-permeable membrane Diffusion of solutes (urea, creatinine, …) from blood into the dialysate contained in the abdominal cavity Removal of excess water (ultrafiltration) due to osmotic gradient generated by glucose in dialysate

59. MODALITIES OF PD 1. Continuous Ambulatory Peritoneal Dialysis (CAPD) Dialysate is present within the peritoneal cavity continuously, except when dialysate is being exchanged Dialysate exchanges are performed three to five times a day, during which time the patient is mobile and able to undertake normal daily activities This is the technique most often used for maintenance peritoneal dialysis in patients with end-stage renal failure CAPD is particularly useful in young children, and in elderly patients with cardiovascular instability.

60. MODALITIES OF PD 2.Nightly intermittent peritoneal dialysis (NIPD ) An automated device is used to perform exchanges each night while the patient is asleep. Sometimes Dialysate is left in the peritoneal cavity during the day in addition, to increase the time during which biochemical exchange is occurring.

61. COMPLICATIONS Peritonitis Infection around catheter site Constipation Pleural effusion Failure of peritoneal membrane function CONTRAINDICATIONS Inability or unwillingness of the patient to learn the technique Previous peritonitis Presence of stoma Active intra abdominal sepsis Abdominal hernias

62. RENAL TRANSPLANTATION Treatment of choice for end-stage renal disease Renal transplantation offers the best chance of long-term survival in patients with end-stage renal disease. It can restore normal kidney function and correct all the metabolic abnormalities of CRF. All patients should be considered for transplantation unless there are active contraindications Kidney grafts may be taken from a cadaver or from a living donor.

63. PRE-TRANSPLANT INTERVENTIONS 1. Matching Matching of a donor to a specific recipient is strongly influenced by immunological factors, since graft rejection is the major cause of failure of the transplant. ABO (blood group) compatibility between donor and recipient is essential, and the degree of matching for major histocompatibility (MHC) antigens-particularly HLA-DR-influences the incidence of rejection. T cells are the major cell involved in graft rejection; cytotoxic antibodies against HLA antigens, which may be present pre-transplant (sensitization), are also important.

64. CTD A cytotoxicity test for these antibodies, and T- and B-cell cross-match tests (donor lymphocytes mixed with patient serum), are performed pre-transplant. Positive tests predict early rejection. Immunotherapy: pre-transplant IV methylprednisolone sodium succinate Cyclosporine Azathioprine

65. SURGERY In the transplant operation, the donor vessels are anastomosed to the recipient iliac artery and vein, and the donor ureter to the bladder

66. PERI-OPERATIVE PROBLEMS Fluid balance. Careful matching of input to output is required. Primary graft non-function. Causes include hypovolemia, acute tubular necrosis or other pre-existing renal damage, hyper-acute rejection, vascular occlusion and urinary tract obstruction. Sepsis (related to immunosuppression).

67. Contraindications Absolute CI Active malignancy Severe Ischemic heart disease Occlusive aorto-illiac diseases Active vasculitis Relative CI Children < 1 yr adults>75 In high risk of disease recurrence Diseases of lower urinary tract Significant comobidity

68. COMPLICATIONS Rejection Infection Hypertension Malignancies (lip, skin, lymphomas, cervical) Recurrence of renal disease Retroperitoneal bleed Arterial stenosis ( graft hypovolemia) Urine leakage

69. MANAGEMENT AFTER TRANSPLANTATION Immunosuppressive therapy is required to prevent rejection. Different therapeutic regimens are used; a commonly used one is triple therapy consisting of prednisolone, plus ciclosporin or tacrolimus and azathioprine. Newer immunosuppressive drugs such as mycophenolate mofetil and rapamycin are increasing in use. Rejection is treated by short courses of very high-dose corticosteroids in the first instance, although other more potent therapies, such as anti-lymphocyte antibodies or plasma exchange, are used in resistant episodes.