Chronic Kidney Disease

Chronic kidney disease Dr Mirna Vucak-Dzumhur Nephrologist 1 Stereotype for CKD? Or… Marlene Dietrich Isaac Asimov Laurence Olivier Kerry Packer Selena Gomez Bobby Fischer Alfred Hitchcock Check your risk for CKD Quick quiz Are you at risk of kidney disease? Tick if you have: • diabetes • high blood pressure • established heart problems (heart failure or heart attack) and/or stroke • family history of kidney failure • obese (Body Mass Index ≥ 30) • smoker • 60 years or older • Aboriginal or Torres Strait Islander origin • history of AKIs If you answered YES to one or more of the above then you are at risk of kidney disease Kidney Fast Facts Kidney Fast Facts Kidney Fast Facts Media Release – 19 Jan 2017 Ms Stafrace (ex CEO): • In 2014-15 kidney disease was the most common single reason for admission to hospital out of a total of 10 million hospital admissions. • • • In total 1.7 million Australians are living with kidney disease. Even more alarming is that 90% of people with kidney disease - which equates to 1.5 million people nationally - don’t even know that they have it, as there are generally no warning signs. “One of the most frightening things about kidney disease is you can lose up to 90% of your kidney function, before experiencing any symptoms – it really is a silent killer,” she said. “At the moment 1 in 10 non-Indigenous Australians are living with clinical signs of kidney disease, while within the Indigenous population this is a heart-breaking 1 in 5.” • “Kidney disease is estimated to cost $2.5 billion per year in direct healthcare costs, while the personal cost to Australians is immeasurable” • The burden of kidney disease is growing. The latest data indicates that there are 22,234 people on dialysis, or living with a transplant in Australia. By 2020 this number is expected to spiral up to 31,589. This is a 60% increase from 2011, and more than quadruple Australia’s projected population growth of 13% for the same period. The number of people whose end stage kidney disease is caused by Type 2 diabetes is projected to double between 2011 and 2020. Learning objectives • Define CKD stages and their relationship to clinical manifestations • Outline the principles of CKD assessment including risk factors for progressive disease • Outline the principles of CKD treatment including reversal or primary process, reducing progression, BP and vascular risk management 10 Overview of kidney function Maintenance of constant extracellular environment excretion of metabolic waste product excretion of water and electrolytes match net intake and endogenous production Hormones secretion regulation of systemic and renal haemodynamics (renin, prostaglandins, bradykinin) RBC production (erythropoietin) calcium, phosphorus and bone metabolism (calcitriol) 2018 UpToDate Overview of kidney function in patient with CKD, some or all functions may be diminished in patient with ESRD, all kidney functions are absent retention of uraemic toxins abnormalities in fluid, electrolyte and mineral (calcium, phosphate) balance anaemia renal bone disease 2018 UpToDate CKD definition Introduced in 2002 by NKF KDOQI; modified by guideline group KDIGO • GFR <60 ml/min/1.73m2, present for >3 months with or without evidence of kidney damage or Evidence of kidney damage with or without decreased GFR present for >3 months: moderately increased albuminuria proteinuria glomerular haematuria history of kidney transplantation pathological abnormality (e.g. abnormal renal biopsy) anatomical abnormalities ( e.g. scarring seen on imaging or polycystic kidneys) Definition and staging of chronic kidney disease in adults 2018 UpToDate GFR and albuminuria stages Definition and staging of chronic kidney disease in adults 2018 UpToDate GFR and albuminuria stages 2018 UpToDate Signs and symptoms in G1 (GFR >90) and G2 (GFR 60-89) • Usually asymptomatic • Signs: moderately and severely increased albuminuria urinary sediment abnormalities (RBC, WBC, hyaline and granular casts) hx of kidney transplantation (CAN, BKVAN, rejection, CNI toxicity, recurrent disease) pathological abnormality (abnormal renal biopsy: glomerular diseases, vascular diseases, tubulointerstitial diseases, cystic disease anatomical abnormalities (scarring seen on imaging or polycystic kidneys) Definition and staging of chronic kidney disease in adults 2018 UpToDate Signs & Symptoms of Stage 3 CKD (3a:GFR 45-59; 3b:GFR 30-44) May have symptoms/signs of CKD, symptoms of comorbidity/ies and complications of CKD or being asymptomatic Symptoms and signs: •fatigue •oedema •muscle cramps or restless legs •urine volume and appearance changes •nocturia •loss of appetite •skin changes: pruritus, dry and flaking skin •diarrhoea or constipation •back (flank) pain Definition and staging of chronic kidney disease in adults 2018 UpToDate Signs & Symptoms of Stage 4 CKD (GFR 15-29) Loss of homeostatic mechanisms Symptoms and signs of volume overload, electrolyte dysbalance, metabolic acidosis, hypertension, anaemia and mineral and bone disorders • • • • • • • • • • • • fatigue sleep problems oedema urine volume and appearance changes loss of appetite diarrhoea or constipation nausea or vomiting changes in taste, metallic taste in the mouth (dysgeusia) difficulty in concentrating peripheral neuropathy restless legs, muscle cramps skin changes: pruritus, dry and flaking skin Definition and staging of chronic kidney disease in adults 2018 UpToDate Constellation of Signs & Symptoms of Stage 5 CKD (GFR <15) - uraemia CVS, GI, respiratory, CNS, PNS, haematology, endocrinology, skin • Anaemia • Easy bleeding and bruising • Fatigue and feeling drowsy • • • • • • • • Weakness Mental symptoms such as lowered mental alertness, trouble concentrating, confusion, seizures Muscle cramps and twitching Numbness in the extremities Nausea, vomiting, loss of appetite Thirst, dysgeusia Diarrhoea Poor digestion (varying degrees of gastroparesis • • Itchy skin, itchy eyes Skin colour changes (sallow) • • • Dyspnoea (due to fluid overload, anaemia) Hypertension Headache • • Nocturia Variable urine output • • Decreased libido Changes in menstrual cycle (and difficulty getting pregnant) 2018 UpToDate Principles of CKD assessment including risk factors for progressive disease Algorithm for initial detection of CKD Kidney health Australia CKD assessment • History (risk factors: DM, HT, CV disease, stones, hereditary causes, FHx) • Physicial examination • Imaging (US, CT KUB, abdo X-ray) • Blood tests (EUC over time, immunology/ vasculitic screen/ hepatitis serology/ myeloma screen) • Urine: dipstick, microscopy, RBC casts and morphology, urinary ACR/ 24 h proteinuria • Renal Bx CKD assessment Glomerular Filtration Rate Measurement versus estimation: 1. GFR measurement: – Measurement of GFR is complex, time consuming, and cumbersome – Inulin ideal (physiologically inert) but expensive, time consuming and not available – alternative filtration markers (such as radioactive or nonradioactive iothalamate, iohexol, DTPA or EDTA) – Clinical indications: chemotherapy; prior to kidney donation; prior to determining the need for pre-emptive transplant 1.Johnson DW, Jones GRD, Mathew TH et al. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: New developments and revised recommendations. Med J Aust 2012;197(4):222-3. 2. 2018 UpToDate GFR Assessment of kidney function: 2018 UpToDate CKD assessment Glomerular Filtration Rate 2. Estimated GFR (eGFR) (mathematically derived from serum creatinine, age, sex and race) • Measurement of creatinine clearance • Estimation equations: – Cockcroft-Gault equation – the Modification of Diet in Renal Disease (MDRD) study equation – the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation » superior when GFR is normal or mildly reduced » usually automatically calculated by the laboratory analysing the blood sample and reported along with the serum creatinine result • The MDRD study and CKD-EPI equations are normalized to body surface area • “Normal” GFR is >90 ml/min/1.73m2 Johnson DW, Jones GRD, Mathew TH et al. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: New developments and revised recommendations. Med J Aust 2012;197(4):222-3. 2018 UpToDate Clinical situations where eGFR results may be unreliable and/or misleading • acute changes in kidney function • people on dialysis • recent consumption of cooked meat (re-assessment after fasting of avoiding a cooked meat meal within 4 hours of blood sampling) • exceptional dietary intake (vegetarian diet, high protein diet, creatine supplements) • extremes of body size • diseases of skeletal muscle, paraplegia, or amputees (may overestimate eGFR) • high muscle mass (may underestimate eGFR) • children under the age of 18 years • severe liver disease • eGFR values > 90 mL/min/1.73m2 • drugs interacting with creatinine excretion (e.g., fenofibrate, trimethoprim) • pregnancy (use serum creatinine instead eGFR) Johnson DW, Jones GRD, Mathew TH et al. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: New developments and revised recommendations. Med J Aust 2012;197(4):222-3. 2018 UpToDate Proteinuria Four basic types of proteinuria: • glomerular proteinuria (albumin) • tubular proteinuria (LMW proteins, beta2-microglobulin, immunoglobulin light chains, retinol-binding protein and polypeptides derived from the breakdown of albumin) • overflow proteinuria (immunoglobulin light chains in MM, lysozyme (in acute myelomonocytic leukemia), myoglobin (in rhabdomyolysis), or free haemoglobin (in intravascular hemolysis) • post-renal proteinuria (infection, tumours) 2018 UpToDate Proteinuria • normal rate:< 20 mg/day (15 mcg/min) – 4 to 7 mg/day (3 to 5 mcg/min) in healthy young adults – increases with age and with an increase in body weight • moderately increased albuminuria ("microalbuminuria") – persistent albumin excretion between 30 and 300 mg/day (20 to 200 mcg/min) – In patients with diabetes, indicative of incipient diabetic nephropathy – In no-ndiabetics, associated with an increased risk for CV disease • overt proteinuria or severely increased albuminuria "macroalbuminuria") - albumin excretion >300 mg/day (200 mcg/min) > standard dipstick becomes “+” Moderately increased albuminuria and cardiovascular disease: 2018 UpToDate Proteinuria • 2 semi-quantitative tests: – Dipstick> reflects glomerular proteinuria “+” when albuminuria >300-500 mg/day • – highly dependent upon urine concentration SSA (sulfosalicylic acid) > detects all protein • used for detection of tubular or overflow proteinuria – • If dipstick neg and SSA positive >?tubular proteinuria Quantitative tests: – The “Gold standard” > 24 h collection for protein and creatinine – ACR (albumin to creatinine ratio) • accurately predicts renal and CV risks in population studies • reduction in urine ACR predicts renoprotective benefit in intervention trials • influenced by creatinine excretion and variable albumin/protein excretion during the day (diurnal) • first morning sample preferable – PCR (protein to creatinine ratio) Australian Bureau of Statistics. Australian Health Survey: Biomedical Results for Chronic Diseases, 2011-12. ABS, Canberra; 2013. 2018 UpToDate Factors other than CKD known to increase urine albumin excretion • • • • • • • urinary tract infection high dietary protein intake congestive cardiac failure acute febrile illness heavy exercise within 24 hours menstruation or vaginal discharge drugs (especially NSAIDs) Australian Bureau of Statistics. Australian Health Survey: Biomedical Results for Chronic Diseases, 2011-12. ABS, Canberra; 2013. 2018 UpToDate Correlation of moderately increased albuminuria (microalbuminuria) with cardiovascular disease • associated with progression of kidneys disease • risk factor for CV morbidity and early CV mortality in both nondiabetic and diabetic patients (clinical trial, population studies-HOPE, LIFE, PREVEND) • mechanism: unclear (generalised endothelial dysfunction likely) – hypothesis: • vasodilatation response reduced • increased plasma level of vWF associated with thrombosis risk • hyperglycaemia induced alterations in extracellular matrix> decreased density of heparan sulfate> increased microvascular permeability> increased albuminuria and lipoprotein deposition 2018 UpToDate CV risk factors associated with CKD Traditional risk factors: 1. 2. 3. 4. 5. Hypertension Hypervolemia Dyslipidemia Sympathetic overactivity Hyperhomocysteinaemia CKD-related risk factors: 1. 2. 3. 4. 5. Anaemia Hyperphosphataemia Hyperparathyroidism Generalized inflammation Proteinuria / albuminuria •both reduced eGFR and significant albuminuria are independent risk factors for CV disease •even early CKD constitutes a significant risk factor for CV events and death •for people with CKD, the risk of dying from CV events is up to 20 X greater than the risk of requiring dialysis or transplantation 2018 UpToDate Kidney Health Australia Kidney Health Australia Absolute CV risk assessment Kidney Health Australia Absolute CV risk assessment Kidney Health Australia Risk factors for progressive disease Clinical predictors of accelerated progression: – increased proteinuria, systemic and intraglomerular hypertension, diabetes, obesity, metabolic syndrome, black race, environmental exposures such as lead, smoking, analgesic agents 2 sets of mechanisms of damage (1) initiating mechanisms specific to underlying aetiology • immune complexes, mediators of inflammation in GN or toxin (2) progressive mechanisms irrespective of underlying aetiology - Hemodynamic: • hyperfiltration, intraglomerular hypertension and hypertrophy of remaining nephrons – increased intrarenal activity of RA axis contribute to: initial adaptive hyperfiltration maladaptive hypertrophy and sclerosis sec to stimulation of TGF- B - Proteinuria Podocytes injury and loss Tubulointerstitial fibrosis Angiotensin II receptor (1B) activation Calcium phosphate precipitation in the renal interstitium Genetic factors 2018 UpToDate Pathogenesis of CKD Nature Reviews Nephrology volume12, pages426–439 (2016) N Engl J Med.2004 Sep 23;351(13):1296-305. Lancet. 2012 Jan 14;379(9811):165-80.; Chaudhry General management of CKD 1. Treatment of reversible causes of renal failure 2. Preventing or slowing the progression of renal disease 3. Treatment of the complications of renal failure 4. Adjusting drug doses when appropriate for the level of eGFR 5. Identification and adequate preparation of the patient in whom renal replacement therapy will be required 2018 UpToDate 1. Treatment of reversible causes of renal failure • decreased renal perfusion – Hypovolemia, hypotension, infection and the administration of drugs which lower the eGFR • administration of nephrotoxic drugs – administration of drugs or diagnostic agents that adversely affect renal function • urinary tract obstruction 2018 UpToDate 2. Slowing the rate of progression Treatment of the underlying disease: Treatment of secondary factors: • • • • • • 1. intraglomerular hypertension and glomerular hypertrophy 2. systemic hypertension (attaining the blood pressure goal 3. proteinuria (attaining proteinuric goal) 4. glycaemic control 5. hyperlipidemia 6. metabolic acidosis 7. dietary adjustments with protein restriction, “renal diet”, smoking cessation diabetes hypertension glomerulonephritis tubulointerstitial diseases obstruction vascular disease 2018 UpToDate Hypertension in CKD • ACEi or ARBs Recommendation: • Diuretics • Treat adult patients without albuminuria to keep office BP consistently ≤140/90 mmHg (without diabetes) • Treat adult patients with any level of albuminuria to keep office BP consistently ≤130/80 mmHg, and include an ACEi or ARB (with and without diabetes) thiazides, loop diuretics, aldosterone antagonists • Beta-blockers • Calcium channel blockers nondihydropyridine and dihydropiridine CARI Commentary on the KDIGO Clinical Practice Guideline for the management of blood pressure in chronic kidney disease, Nephrology 19 (2014) 53–55 KHA-CARI Commentary on the KDIGO Clinical Practice Guideline for the management of blood pressure in chronic kidney disease, Nephrology 19 (2014) 53–55 Glycaemic control Recommendation: • Optimal glycaemic control significantly reduces the risk of developing microalbuminuria, macroalbuminuria and/or overt nephropathy in DM (1&2) • The definition of ‘optimal’ vary depending on the balance between benefits and risks and the individual’s priorities • Target BSL and HbA1c : – 6-8mmol/L fasting – 8-10 mmol/L postprandial – HbA1c: ≤7% (range 6.5-7.5) – Needs individualisation according to patient circumstances (disease duration, life expectancy, comorbidities and established vascular complications) KHA – CARI Guidelines General Practice Management of Type 2 Diabetes - 2014-15 2018 UpToDate Lipid management in CKD • In adults with newly identified CKD, recommended evaluation with a fasting lipid profile. • Consider secondary causes if severely elevated fasting lipid levels (LDLcholesterol >4.9 mmol/L or triglycerides >11.3 mmol/L) (nephrotic syndrome, hypothyroidism, diabetes) • Follow-up measurement of lipid levels is not required for the majority of patients. • If aged ≥50 years with any stage of CKD (irrespective of lipid levels): - Statin if eGFR > 60 mL/ min/1.73m2 Statin or statin/ezetimibe combination if eGFR ≤ 60 mL/ min/1.73m2 . • If aged < 50 years with any stage of CKD (irrespective of lipid levels): - Statin if presence of one or more of: CAD, previous ischaemic CVA, diabetes or estimated 10-year incidence of fatal or non-fatal myocardial infarction > 10% • Lifestyle advice if hypertriglyceridaemia is present. KHA-CARI commentary on the KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease Nephrology 19 (2014) 663–666 Protein restriction • Dietary protein restriction has been shown to result in modest slowing of CKD progression • However, the beneficial effect of protein restriction is typically outweighed by the deleterious effects of nutritional restriction Recommendation: • patients with progressive CKD should have individualised diet intervention involving an appropriately qualified dietitian • adults with early CKD should consume a normal protein diet, consisting of 0.75 - 1.0 g/kg/day, with adequate energy (Recommended Daily Intake (RDI)(1C) • low protein diet (0.6 g/kg/day) to slow down CKD progression is not recommended due to the risk of malnutrition (1C) • people with excess protein should reduce their intakes to the RDI levels as a high protein diet may accelerate renal function decline in mild renal insufficiency (2C) CARI Guidelines More guidelines… Acidosis: Management • Supplementation with sodium bicarbonate (SodiBic 840 mg capsule) -starting dose: 1 capsule od or bd, -increasing up to 2 tablets bd if needed -titrating to keep the HCO3 level >22mmol/L Risk: fluid overload increased sodium load may worsen BP control Anaemia: when eGFR <60 mL/min/1.73m2 Target: Hb 100 – 115 g/L iron supplementation: Ferritin >100 µg/L; TSAT >20% Once ESA commenced, maintain: Ferritin 200-500 µg/L; TSAT 20-30% CARI Guidelines Chronic kidney disease: Sultan Chaudhury; Circulation. 2007 Jul 3;116(1):85-97. Nat Rev Nephrol. 2011 Mar;7(3):128-3, Nephrol Dial Transplant. 2002 May;17(5):723-31 Lancet. 2012 Jan 14;379(9811):165-80. Levey AS, Stevens LA, Coresh J. Conceptual model of CKD: applications and implications. Am J Kidney Dis 2009 Thank you! 50