Diagnostic Assessments Relating to Renal Function: Why we do them? What do they mean? Mohamud Karim MD, FRCPC. Feb 27, 2015

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1 Diagnostic Assessments Relating to Renal Function: Why we do them? What do they mean? Mohamud Karim MD, FRCPC Feb 27, 2015 Acknowledgements: Previous presentor

2 Why are Patients Referred? Renal Syndromes: Abnormalities in blood &/or urine tests Declining GFR Hematuria Proteinuria Nephrotic Syndrome Nephritic Syndrome Acute Kidney Injury Chronic Kidney Disease Multi-system Illnesses

3 WHY TEST? DIAGNOSIS/TREATMENT? SYNDROME PATHOLOGY DISEASE TREATMENT

4 Initial Consultation by Nephrologist History Physical Exam Basic Labs Extra Labs Radiology Biopsy

5 Initial Consultation by Nephrologist Routine testing for proper assessment CBC, Sodium, Potassium, Bicarbonate, Urea, Creatinine, egfr Urinalysis and microscopy Calcium, Phosphorus, (Parathyroid hormone) Additional PRN tests: Serum protein electrophoresis Hepatitis serology and HIV testing Renal ultrasound ANA, ANCA, ESR, CRP, C3, C4.

6 Further Diagnostic Tests Renal biopsy Vascular studies Ultrasound studies Radiologic studies Renal MRI and CT Cystographic studies

7 Evaluation Knowledge of Renal System is Key

8 CBC HGB -: N Target in CKD: Useful for Diagnosis Acute versus Chronic Hemolysis Myeloma Look for other causes Iron Deficiency WBC Responsible for fighting infection and/or other foreign materials. PLATELETS giga/L determining risk of invasive procedure (i.e. kidney biopsy) Low platelets importnant in AKI TTP/HUS

9 Renal Function Assessment: Cr and EGFR

10 GFR

11 Glomerular Filtration Rate Sum of all nephron filtration rates Best index of overall function Reduction implies a problem Translatable concept Equates to percentage Kidney function

12 Creatinine

13 Serum Creatinine: Problems Non-renal influences Gender, ethnicity, age and muscle mass Nutrition/diet Drugs (e.g. cimetidine) Clinical utility Poor sensitivity for CKD Not useful in ARF Muscle wasting disorders and amputees Analytical problems Non-specificity (protein, ketones, ascorbic acid) No international standardization Spectral interferences (icterus/lipaemia/haemolysis)

14 Creatinine/GFR

15 Serum creatinine (µmol/l) Serum Creatinine Hides Early Renal Damage CKD stage 0 Proportion misdiagnosis GFR (ml/min/1.73m 2 ) Reproduction from the late David Newman

16 GFR Prediction Equations Cockcroft-Gault formula C cr (ml/min) = 1.23 x (140-age) x weight/p cr (x 0.85 if female) MDRD Study equation GFR (ml/min/1.73 m 2 ) = 186 x [(P cr )/88.4] x (age) x (0.742 if female) x (1.210 if African American) Cockcroft & Gault. Nephron 1976; 16: Levey AS, et al. Ann Intern Med 1999;130:

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18 Chronic Renal Failure Markers Urea (Ur) mmol/l Principal end product of protein break down Rises with decreasing GFR Creatinine (Cr) umol/l End product muscle breakdown Marker of degree of kidney disease Cr and Ur usually rise in tandem in chronic and ESRF, but Urea levels can remain low or normal if patient is malnourished with a low protein intake. There is no set value with renal decline.

19 Classification of CKD waking up to the impact of proteinuria Stage 1: Stage 2: Stage 3A: GFR Stage 3B: GFR GFR>90 + abnormal urinalysis GFR abnormal urinalysis Stage 4: GFR Stage 5: GFR <15 or dialysis dependent Suffix P denotes presence of proteinuria (ACR>30 or PCR>50)

20 NICE 2008: Diagnosis of CKD Proteinuria=ACR>30 or PCR>50 (NOT dipstick) 3 egfr estimations <60 over a period not less than 90 days Progressive decline defined as egfr falling by >5mls/min/year Focus on those whose observed rate of decline would necessitate RRT within their lifetime

21 Urinalysis and microscopy Hematuria Marker of true glomerular disorder Kidney, ureter or bladder cancer Kidney stones Polycystic kidney disease Proteinuria Important glomerular disorder Often high in severe diabetic nephropathy and sometimes with hypertension alone Predicts risk of developing ESRD ACR and Screening Casts Marker of glomerular or tubular disorder

22 What is Microalbuminuria? Definitions and prevalence Microalbuminuria is found in: 5-7% of the healthy population 1, % of the hypertensive population 1,3,4 25%-40% of people with diabetes 1,5 Comparison of tests Normal Microalbuminuria Macroalbuminuria (clinical proteinuria) uacr (mg/mmol) <2.5 (males) < 3.5 (females) < (males) < (females) upcr (mg/mmol) Dipstick < /trace > /++ 1.Yuyun et al. Current Opinion in Nephrology and Hypertension 2005;14(3): Hillege et al. J Internal Medicine : (PREVEND) 3. Garg et al. Kidney International (NHANES-III) Atkins et al. Kidney International Supplement (AUSDIAB) Wachtell et al. Am Heart J. (LIFE) RA/RCP Joint CKD Guidelines 2006

23 Chemistry Profile Urea (Ur) mmol/l Uremia causes nausea, vomiting, metallic taste in mouth, headache, and high potassium levels Creatinine (Cr) umol/l Only elevates in renal failure, will rise as kidney s decline GFR umol/l men, women Meaningless if patient on dialysis Albumin (alb) g/l Is a marker of nutritional status; low indicates to increase dietary protein Sodium (Na+) mmol/l Main electrolyte which determines volume status

24 Chemistry Potassium (k+) mmol/l Minor changes have significant consequences Magnesium (Mg) mmol/l Low levels may be low due to malnourishment Chloride (Cl--) mmol/L Plays a role in sodium and water balance Bicarbonate (HC03) mmol/l Measured as CO2 in some labs

25 Mineral Metabolism Calcium (Ca+) mmpl/L Abnormalities begin early in renal insufficiency. Long term effects include bone disease & metastatic calcification. Phosphorus (PO4) mmol/l Normal PO4and Ca+ is essential to prevent osteodystrophy PTH pmol/L (often 2-3x normal value for RRT) Often elevates as kidney function declines. Low Ca+, high Phos, and low calcitrol stimulates PTH secretion, which, in turn releases Ca+ from the bones into the blood stream, resulting in abnormal bone turnover. Resistance to PTH may develop in kidney disease resulting in parathyroid surgical intervention.

26 IRON PANEL Serum Iron 9-32umol/L Iron is essential for ESA therapy TIBC 45-81umol/L The amount iron that can be bound to transferrin Ferritin greater than 100 in Renal Refers to transferrin bound iron. T Sat greater than 20% in Renal Useful indicator combined with Ferritin (changes with infection, inflammation)

27 Routine Blood Tests by Category CBC Lytes CRF Marker Nutrit. Anemia Mineral Metabolis Glucos Infectio n Control Immune /Other. wbc Na Ur Alb hgb Ca FBS HB s Ag SPEP hgb K Cr Retics PO 4 RBS Anti- HBs UPEP hct Cl GFR Se Fe Alk Phos HbA1c HB c AB ANA plt HCO 3 - TIBC PTH HCV ANCA Mg Tsat HIV C3,C4 Transferri n Anti GBM ab Ferr

28 Serum protein electrophoresis Multiple myeloma Fairly common cause of CKD and ESRD Amyloidosis Primary Secondary to longstanding low GFR Chronic inflammation Lupus

29 Other Diagnostic Tests

30 Renal biopsy Common indications Rapidly declining kidney function NYD Severe or persistent proteinuria Hematuria with other signs of Kidney disease Acute kidney failure, unexplained Acute rejection to Transplant

31 Radiologic Studies Ultrasound Nuclear Renogram CT scanning Magnetic Resonance Imaging Renal arteriography Renal venogram Voiding cystourethrogram Retrograde pyelogram

32 Renal Ultrasound Why have a Renal Ultrasound? Mass-detection and staging of renal tumors. Obstruction Anatomy Frequent UTI s Kidney Size

33 Renal Angiography Invasive assessment of arterial flow (Uses contrast) Much more detailed Additional conditions under which the test may be performed: Acute arterial occlusion of the kidney Acute renal failure Atheroembolic renal disease Renal artery stenosis Renal cell carcinoma

34 CT or MRI Angiogram Non invasive assessment of arterial flow into kidneys Renal artery stenosis Fibromuscular dysplasia Generalized atherosclerotic changes Long standing HTN Smokers Absence of flow altogether i.e.. Arterial thrombosis

35 CT of Kidneys The abdominal CT scan may reveal the following kidney problems: Obstructive uropathy Complicated UTI (pyelonephritis) Kidney stones Kidney swelling (hydronephrosis) Kidney or ureter damage Polycystic kidney disease

36 Urology Tests Cystoscopy Used to detect urinary disorders Done if abnormal urine cytology Retrograde pyelogram Used to diagnose chronic obstruction Lower anatomy abnormalities Pyelonephritis

37 Monitoring of declining Renal Function Monthly labs Anemia Iron deficiency Calcium high or low PO4 high or low PTH high or low Urea levels marker of inadequate dialysis PRU want greater than 66% generally Albumin marker of overall health and may also acute decrease in acute illness Uric acid higher risk of gout + increases HTN

38 Indications to start some form of dialysis (or pre-emptive transplant) Unmanageable hyperkalemia Severe metabolic acidosis Uremia symptomatic Uremic pericarditis High urea levels may cause inflammation of pericardial tissue may cause cardiac tamponade if not aggressively treated Pulmonary edema or severe peripheral edema not amenable to maximal medical therapy

39 Questions