5.Chronic kidney disease.Dr.Thilak Jayalath_Renal Lectures.
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5.Chronic kidney disease.Dr.Thilak Jayalath_Renal Lectures.



chronic renal failure

chronic renal failure



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    5.Chronic kidney disease.Dr.Thilak Jayalath_Renal Lectures. 5.Chronic kidney disease.Dr.Thilak Jayalath_Renal Lectures. Document Transcript

    • 1 Chronic kidney disease  Chronic kidney disease (CKD) is the clinical syndrome of the metabolic and systemic consequences of a gradual, substantial, and irreversible reduction in the excretory and homeostatic functions of the kidneys  CKD is defined as either kidney damage or a decreased kidney glomerular filtration rate (GFR) of <60 mL/min/1.73 m2 for 3 or more months CKD in Sri Lanka  Number of CKD cases are increasing  Most common cause could be chronic glomerulonephritis  Cause for higher number of CKD cases in certain parts of the country is not known, but could be multi factorial  With ever increasing number of diabetes mellitus, diabetic nephropathy leading to CKD becoming common  With limited facilities for renal replacement therapy , most patients with CKD die early Stages of Chronic Kidney Disease Stage GFR ml /min Descriptor 1 > 90 Kidney disease with normal or increased GFR 2 60 - 89 Kidney disease with mildly reduced GFR 3 30 - 59 Moderately severe renal failure 4 15 - 29 Severe renal failure 5 < 15 End – stage renal failure  Established renal failure (also called end-stage renal failure, ESRF) is the situation in which dialysis is required to sustain life of any reasonable quality  Patients with CKD stage 3 or lower (GFR >30 mL/min) generally are asymptomatic  Uremic manifestations in patients with CKD stage 5 are believed to be secondary to an accumulation of toxins, the identity of which is generally not known Common causes of CRF • Diabetes Mellitus • Glomerulonephritis ( chronic ) • Pyelonephritis (chronic) • Polycystic kidney disease • Hypertension • Renovascular disease Dr.Thilak Jayalath MBBS MD FRCP FRCPE FISN Senior Lecturer in Medicine & Consultant Physician Department of Medicine, Peradeniya • SLE • Myeloma • Nephrocalcinosis • Scleroderma • Amyloidosis • Renal tumours •• Renal Tuberculosis
    • 2 Various factors affecting the progression of CRF • Age of onset • Male gender • Race Various factors affecting the progression of CRF • Genetic factors • Proteinuria • Dyslipidaemia • Hypertension • Cigarette smoking Signs and symptoms of chronic kidney disease • Patients with CRF can present with modest or no symptoms, or as a Uraemic emergency • In about one-third of cases, the need for dialysis is imminent by the time the patient is seen in a renal unit SSyymmppttoommss • Malaise • Anorexia • Insomnia • Nocturia and polyuria • Itching • Nausea, vomiting & diarrhoea SSiiggnnss • Short stature • Pallor • Hyperpigmentation • Brown discolouration of nails • Scratch marks • Purpura / bruising • Bone pain • Menorrhagia • Symptoms of carpel tunnel syndrome • Impotence • Infertility •• Convulsions • Hypertension and complications • Signs of fluid overload • Pericardial friction rub • Mixed peripheral neuropathy • Carpel tunnel syndrome •• Proximal myopathy
    • 3 Investigations Assessment of GFR • Diagnose CKD • Assess the severity of CKD Assessment of GFR with Creatinine clearance (CC) Creatinine clearance Methods CC = U V / P U = Urinary creatinine, V = Urinary volume, P = Plasma creatinine Calculation of Creatinine clearance Methods Cockcroft - Gault formula K x [140 – age (years)] x weight (kg) Plasma creatinine (µmol/l) K - Women - 0.85 Men - 1.23 Limitation of creatinine clearance to assess GFR • With progressive renal failure tubular excretion of creatinine is increased • This will lead to overestimate of GFR • Certain drugs like Cimetidine, Spironolactone inhibit tubular excretion of creatinine The most accurate estimation of GFR involves measurement of clearance of radiolabelled EDTA or Iohexol, a non ionic contrast medium 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 with normal blood glucose is common in CRF Urine microscopy
    • 4  White cells in the urine usually indicate active bacterial urinary infection, but this is an uncommon cause of renal failure; sterile pyuria suggests papillary necrosis or renal tuberculosis  Eosinophiluria is strongly suggestive of allergic tubulointerstitial nephritis or cholesterol embolization  Granular casts are formed from abnormal cells within the tubular lumen, and indicate active renal disease  Red-cell casts are highly suggestive of glomerulonephritis Urine biochemistry Urine osmolality is a measure of concentrating ability A low urine osmolality is normal in the presence of a high fluid intake but indicates renal disease when the kidney should be concentrating urine, such as in hypovolaemia or hypotension Urine electrophoresis and immunofixation is necessary for the detection of light chains, which can be present without a detectable serum paraprotein Urine culture This should always be performed Early-morning urine samples should be cultured if tuberculosis is possible Blood biochemistry Urea - disproportionately high level seen in percatabolism and dehydration Creatinine - elevated in all cases of CKD Potassium - high level seen in severe CKD. Indicates potential cardiotoxicity and response to ACE inhibitors Bicarbonate - reduced level in metabolic acidosis Calcium - reduced in renal osteodystrophy Phosphate - increased in renal osteodystrophy Parathyroid hormone - increased in renal osteodystrophy Haematology Haemoglobin is to assess the need for erythropoietin Eosinophilia suggests vasculitis, allergic tubulointerstitial nephritis, or cholesterol embolism. Markedly raised viscosity or ESR suggests myeloma or vasculitis Fragmented red cells and/or thombocytopenia suggest intravascular haemolysis due to accelerated hypertension, haemolytic uraemic syndrome or thrombotic thrombocytopenic purpura Immunology Complement components may be low in active renal disease due to SLE, mesangiocapillary glomerulonephritis, post-streptococcal glomerulonephritis, and cryoglobulinaemia
    • 5 Autoantibody screening is useful in detection of scleroderma Wegener's granulomatosis and microscopic polyangiitis and Goodpasture's syndrome Cryoglobulins should be sought in patients with unexplained glomerular disease, particularly mesangiocapillary glomerulonephritis Antibodies to streptococcal antigens (ASOT, anti-DNase B) should be sought if post- streptococcal glomerulonephritis is possible Antibodies to hepatitis B and C may point to polyarteritis or membranous nephropathy (hepatitis B) or to cryoglobulinaemic renal disease (hepatitis C) Antibodies to HIV raise the possibility of HIV-associated renal disease Electrophoresis and immunofixation should be performed for myeloma. Imaging Ultrasound - every patient should undergo ultrasonography (for renal size and to exclude hydronephrosis) Plain abdominal radiography and CT (without contrast) to exclude low-density renal stones or nephrocalcinosis, which may be missed on ultrasound 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 Rugger jersey appearance Macroscopic Appearance in CRF Renal Biopsy This should be performed in every patient with unexplained renal failure and normal sized kidneys, unless there are strong contraindications Complications of CKD • Incresed incidence of cardiovascular disease • Anaemia • Renal osteodystrophy • Endocrine abnormalities • Neurological complications • Increased rate of infections • Dermatological abnormalities • Psychological manifestations •• Malnutrition
    • 6 • Metabolic abnormalities • Gastrointestinal tract abnormalities Anaemia Renal anaemia, which is normochromic and normocytic, accounts for many of the symptoms that previously were attributed to uraemia. These include lethargy, cold intolerance, and loss of stamina Factors contributing to renal anaemia • Relative deficiency of erythropoietin • Reduced RBC survival as a result of haemolysis or hypersplenism • ‘Uraemic inhibitors’ of erythropoiesis • Hyperparathyroidism with marrow fibrosis Factors contributing to renal anaemia • Aluminium toxicity • Iron/folate deficiency • Blood loss • Bone marrow toxins Renal osteodystrophy The term 'renal osteodystrophy' embraces the various forms of bone disease that may develop alone or in combination in chronic renal failure • hyperparathyroid bone disease • osteomalacia, • osteoporosis, • osteosclerosis • adynamic bone disease  Problems of renal osteodystrophy can develop early and patients with a glomerular filtration rate (GFR) of 60 ml/minute/1.73m2 are at risk and should be evaluated  Renal osteodystrophy manifest as bone pain, deformity, pathological fractures, soft tissue and especially vascular calcification, and proximal myopathy Pathogenesis of renal osteodystrophy • Reduced activation of vitamin D receptors in the parathyroid glands leads to increased release of parathyroid hormone • 1, 25-Dihydroxycholecalciferol deficiency also results in gut calcium malabsorption
    • 7  Phosphate retention owing to reduced excretion by the kidneys, also indirectly by lowering ionized calcium (and probably directly via a putative but unrecognized phosphate receptor), results in an increase in PTH synthesis and release  PTH promotes reabsorption of calcium from bone and increased proximal renal tubular reabsorption of calcium, and this opposes the tendency to develop hypocalcaemia induced by 1, 25-(OH)2D3 deficiency and phosphate retention  This 'secondary' hyperparathyroidism leads to increased osteoclastic activity, cyst formation and bone marrow fibrosis (osteitis fibrosa cystica) Endocrine abnormalities  Hyperprolactinaemia, which may present with galactorrhoea in men as well as women  Increased luteinizing hormone (LH) levels in both sexes and abnormal pulsatility of LH release  Decreased serum testosterone levels (only seldom below the normal level); sexual dysfunction and decreased spermatogenesis are common  Absence of normal cyclical changes in female sex hormones, resulting in oligomenorrhoea or amenorrhoea  Complex abnormalities of growth hormone secretion and action, resulting in impaired growth in uraemic children (pharmacological treatment with recombinant growth hormone and insulin-like growth factor is used)  Abnormal thyroid hormone levels, partly because of altered protein binding Metabolic abnormalities  Urate retention is a common feature of chronic renal failure. This leads to gout  Treatment of clinical gout is complicated by the nephrotoxic potential of NSAIDs.  Colchicine is useful in treatment of the acute attack, and allopurinol should be introduced later under colchicine cover to prevent further attacks  The dose of allopurinol should be reduced in renal impairment  Insulin is catabolized by and to some extent excreted via the kidneys  For this reason, insulin requirements in diabetic patients decrease as renal failure progresses Lipid abnormalities are common in renal failure  Impaired clearance of triglyceride-rich particles  Hypercholesterolaemia (particularly in advanced renal failure). Dermatological abnormalities  retention of nitrogenous waste produts  hypercalcaemia
    • 8  hyperphosphataemia  elevated calcium × phosphate product  hyperparathyroidism (even if calcium and phosphate levels are normal)  Iron deficiency Gastrointestinal complications • decreased gastric emptying and increased risk of reflux oesophagitis • increased risk of peptic ulceration • increased risk of acute pancreatitis • constipation - particularly in patients on continuous ambulatory peritoneal dialysis (CAPD) Neurological abnormalities • Asterixis • Tremor • Myoclonus • Convulsions Management Clinical approach to the patient with CRF 1. Is there any life threatening complication of CRF? 2. Does the patient have CRF? 33.. Are there factors , operating which have caused or are causing acute reduction in chronically impaired renal function ? 4. What is the cause of CRF 5. What measures are needed to delay progression? 6. Are there complications of CRF that require specific treatment? (1) Is there any life threatening complication of CRF? • Hyperkalaemia • Metabolic acidosis • Pulmonary oedema • Severe anaemia (2) Does the patient have CRF?  History > 6 months ill health, long standing hypertension, proteinuria, nocturia for > 6 months  Pallor, pigmentation, pruritus, brown nails, evidence of long standing hypertension  Normochromic anaemia , small kidneys on ultrasound ( except : diabetes , amyloid , myeloma , adult polycystic kidney disease ), renal osteodystrophy on radiography • Peripheral neuropathy • Carpel tunnel syndrome •• Autonomic dysfunction
    • 9 (3) Are there factors, operating which have caused or are causing acute reduction in chronically impaired renal function? Renal hypotension  Dehydration from diarrhoea, diuretics, surgery  Cardiac failure  Pericardial tamponade  Renal vascular disease  Drugs, especially ACE inhibitors + NSAIDS  Systemic infection Obstruction and infection of the urinary tract • Papillary necrosis and sloughing • Stones • Bladder cancer • Polycystic cysts Metabolic and toxic • Hypercalcaemia • Hyperuricaemia • Contrast media • Drugs Progression of underlying diseases Relapse of nephritis Development of accelerated phase of hypertension Renal vein thrombosis usually in chronically nephrotic patients (4) What is the cause of CRF? • Diabetes • Glomerulonephritis • Pyelonephritis • Polycystic kidney • Hypertension • Renovascular (5) What measures are needed to delay progression of CKD? Dietary restriction of protein Treatment of Hypertension Good glycaemic controll in patients with DM Treatment of hyperlipidaemia
    • 10 Avoidance of nephrotoxic drugs Dietary restriction of protein Dietary manipulation (low-protein diet) has long been advocated as a means of retarding CRF Treatment of hypertension Diuretics - Loop diuretics are more effective ACE inhibitors - Effective, Specially in diabetes mellitus (May decrease GFR in advanced CRF, renal artery disease) Calcium channel blockers - Reduce proteinuria? - Non - Dihydropyridine ones are preffered Treatment of underlying disease • If the CKD is due to diabetes mellitus, good glycemic controll retards the progression of CKD • Treatment of hyperlipidemia to target levels • Avoidance of nephrotoxins - IV radiocontrast, nonsteroidal anti-inflammatory agents, aminoglycosides (6) Are there complications of CRF that require specific treatment? o Prevention of progressive changes in the arteries and heart associated with uraemia may be possible by correction of recognized cardiovascular risk factors Currently accepted strategies • cessation of smoking and other healthy lifestyle modifications • treatment of hypertension • treatment of lipid abnormalities • treatment of anaemia • tight glycaemic control in patients with diabetes • control of plasma calcium and phosphate levels • management of hyperparathyroidism Anaemia Management of renal anaemia is based on administration of erythropoietin with iron therapy Current recommendations suggest that erythropoietin therapy should be commenced once the haemoglobin concentration declines below 10 g/dl and the recommended target haemoglobin concentration in dialysis patients is about 11–12 g/dl The drug is best given subcutaneously
    • 11 The usual starting dose is about 2000 units two or three times per week; Ideally Haemoglobin level should rise by 1 g / dl per month A reticulocyte response is obtained within 3–4 days of starting treatment, and the haemoglobin concentration usually begins to increase from 2 weeks onwards Benefits of Erythropoietin therapy • Amelioration of the symptoms of Anaemia • Reduction of high cardiac output • Increased peripheral vascular resistance • Improvement in myocardial ischaemia • Reduced left ventricular mass Renal Osteodystrophy The mainstay of prevention and treatment of renal osteodystrophy is the maintenance of normal blood divalent ion concentration (particularly phosphorus) Biochemical and radiological monitoring is essential It is best to start treatment early, when creatinine clearance declines to about 40 ml/minute At this stage, dietary reduction of phosphate with an adequate calcium intake may be effective Phosphate binders Calcium carbonate or calcium acetate, 2–8 g/day, is currently the binder of choice Sevelamer hydrochloride (RenaGel – a non-absorbable polymeric phosphate binder) is a promising new agent ( It is calcium-free and binds phosphate through ion exchange and hydrogen binding) Suppression of PTH Treatment with oral calcitriol can be titrated according to PTH levels; the dose usually ranges from 0.25 µg on alternate days to 1 µg/day Combined use of calcium salts and calcitriol increases the risk of hypercalcaemia, and regular blood monitoring is therefore required Dermatological manifestations Pruritus is the most exasperating symptom A number of explanations are advanced including sensitivity to histamines, a raised calcium phosphate product, and uraemia itself
    • 12 Treatment includes starting or increasing dialysis, applying skin emollients, controlling the plasma phosphate level, keeping cool, and the prescription of antihistamines, for example chlorphenamine (chlorpheniramine) 4 mg at night (which is also slightly sedative) Naltrexone, an opioid antagonist, and ultraviolet phototherapy are effective in the short- term