Practices. Special practices:

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1 Practices Special practices: DIALYSIS Tutor: Péter Studinger Location: Fresenius Medical Care Dialysis Unit - First Dept. of Medicine Meeting point: 3rd floor, First Dept. of Medicine PLASMAPHERESIS Tutor: Anna Tremmel Location: First Dept. of Medicine Meeting point: Lecture Hall, First Dept. of Medicine RHEUMATOLOGY Location: Rheumatology Center, Betegápoló Irgalmasrend Budai Kórháza (Bp. Árpád fejdelem útja 7. ) Meeting point: 4 th floor conference room (tárgyaló)

2 Group Dialysis Plasmapheresis Rheumatology Group Dialysis Plasmapheresis Rheumatology

3 Approach to the patient with renal disease Péter Studinger M.D. Ph.D. Semmelweis University, First Department of Medicine 15/09/2017

4 Evaluation of renal disorders - overview Laboratory investigations Glomerular function Tubular function Urinalysis Imaging techniques Renal biopsy

5 Estimation of glomerular function - GFR Creat = 100 μmol/l GFR 52 ml/min GFR 147 ml/min Creatinin clearance (ml/min) = U creat mol/l * X ml Se creat mol/l * 1440 min

6 Relationship between estimated GFR and age

7 Cockroft-Gault formula: Estimation of GFR Ccr (ml/min) = Ccr (ml/min) = (140-age) * weight * creat (140-age) * weight * creat * 0.85 women men MDRD formula / CKD-EPI formula: online calculators gender, age, ethnicity, creat, (BUN, alb) GFR = (Ccr + Curea) / 2

8 Serum Cystatin C Estimation of glomerular function 13kD protein, steady production (housekeeping) Free filtration, no reabsorption. Tubular metabolism ineligible for direct measurement of clearance Independent of age, gender, muscle mass Inflammation, obesity, thyroid disorders, tumors may influence serum level More sensitive marker of moderate renal damage than Se cr.

9 Measurement of tubular Na-reabsorption Fractional Na-excretion (Fe Na ) Fe Na (%) = U Na * P cr P Na * U cr * 100 Healthy person: GFR: 180 L/day, Se Na : 150 mmol/l filtered Na: mmol/day Urinary Na-excretion < mmol/day Fe Na < 1 % Hypovolemic person with normal renal function: Urine Na-excretion: < 20 mmol/day Fe Na < 0.1 %

10 Measurement of tubular Na-reabsorption Clinical relevance: distinction of acute renal failure of prerenal origin and acute tubular necrosis Renal failure due to hypovolemia (prerenal failure): GFR: 14 L/day, Se Na : 150 mmol/l Urinary Na-excretion < 20 mmol/day Fe Na < 1 % filtered Na: 2100 mmol/day Renal failre due to tubular damage (acute tubular necrosis): Urinary Na-excretion > 40 mmol/day Fe Na > 2 %

11 Measurement of renal concentration capacity Morning urine specific gravity > 1022, Osm > 800 mosm/l = normal Water deprivation test over hours - measurement of urine quantity and osmolality hourly, - measurement of serum Na + and osmolality every 2 hours Result: Urine osmolality > 600 mosm/l = physiologic response Urine osmolality unchanged, serum osmolality increases (> mosm/l) = lack of ADH effect (DI) STOP, if body weight decreases by more than 3%! Distinction between central and nephrogenic diabetes insipidus - 40 µg nasal DDAVP (Adiuretin) / 5 IU sc. Vasopressin - urine osmolality increases = central DI, unchanged = nephrogenic DI

12 Measurement of renal acid secretion capacity Clinical relevance: diagnosis of distal renal tubular acidosis Acid load: 0.1 g/kg ammonium-chloride - Urine ph measurement every 2 hours for 6 hours Result: Urine ph < 5.3 = physiologic response Plasma HCO 3- < 18 mmol/l = physiologic response

13 Urine: the fountain of information

14 Urinalysis Colour: orange: rifampicin pink: urate crystals red: macroscopic hematuria, hemoglobin, myoglobin, phenytoin, beets brown: bilirubin, chloroquin, nitrofurantoin green: methylene blue, amitryptiline, propofol darkens upon standing: porphyria Turbidity: pyuria, chyluria, hematuria Odour: urinary infection, ketonuria, rare metabolic disorders Specific gravity: g/l ph < 6.5 underestimation, protein >7.0 g/l overestimation 1010 g/l: isosthenuria Osmolality: mosm/l

15 Urinalysis Dipstick: ph: 4,5-8 Hemoglobin Protein: Dipstick detects albumin Nitrite Leukocyte Glucose Ketones

16 Detection of microalbuminuria Sample Method Screening Morning urine sensitive dipstick (pl. Micral Test II) Morning urine albumin-creatinin ratio (ACR), 24-hour collected urine albumin excretion rate (mg/24h) Confirmation: 2/3 positive samples over 3-6 months Morning urine albumin-creatinin ratio 24-hour collected urine albumin excretion rate (mg/24h) False positive results Urinary tract infection, fever, heart failure, strenuous exercise, uncontrolled diabetes, NSAID abuse

17 Urinary albumin / protein excretion Dipstick Urinary albumin excretion (mg/24h) Alb/creat ratio (mg/mmol) Urinary protein excretion (mg/24h) Protein/creat ratio (mg/mmol) Healthy < 30 < 3 < 150 < 15 Microalbuminuria trace Proteinuria significant nephrotic + > 300 > 30 > 450 > > 700 > 70 > 1000 > > 3500 > 350

18 Proteinuria Sulphosalycilic acid Qualitative: ELFO (pl. SDS-PAGE) Immunelectrophoresis Bence-Jones protein NGAL (neutrophil gelatinase-associated lipocalin)

19 Urine sediment Red blood cells White blood cells UTI /gynecologic infection acute interstitial nephritis cholesterol embolisation Tubule cells acute tubular necrosis acute interstitial nephritis allograft rejection

20 Urine sediment Urothel healthy, infection, urolithiasis, malignancy Squamous cells contamination Oval fat bodies significant proteinuria Casts, crystals, microorganisms

21 Hematuria Macroscopic hematuria Microscopic hematuria high-power field >3 RBCs

22 - Non-glomerular: isomorph Strenuous exercise (marathon running) Urolithiasis Infection Tumor Trauma Polycystic kidney disease Benign prostate hyperplasia Endometriosis Sickle cell anemia (papillary necrosis) Hypercalciuria, hyperuricosuria Coagulopathy - Glomerular: dysmorph Glomerulonephritis Hematuria

23 Casts in the urine Stuctures embedded in Tamm-Horsfall glycoprotein matrix Hyalin cast Lipid cast Tubule cell cast RBC cast ATN cast WBC cast

24 Crystals in the urine Ca-ox dihydrate Ca-ox monohydrate Ca-carbonate Struvite (Mg-amm-phosphate) Cystine Urate

25 Renal ultrasound Size? Thickness of the parencyma? Echogenicity of the parencyma? Surface? Pyelon? Cyst? Stone? Tumor? 9-13cm > 10mm same as the healthy liver smooth without dilation absent liver

26 Renal ultrasound liver Small (7 cm), hyperechogenic kidney chronic kidney disease

27 Renal ultrasound Kidney with uneven surface and narrow parenchyma - chronic pyelonephritis

28 Renal ultrasound Medium-grade hydronephrosis

29 Renal ultrasound Kidney stones with acoustic shadowing and hydronephrosis

30 Renal ultrasound Polycystic kidney disease

31 Renal ultrasound Renal artery Doppler ultrasound Indication: - renal artery stenosis Limitations: - difficult - time-consuming Normal blood flow Renal artery stenosis (tardus et parvus flow)

32 Plain (KUB) X-ray and iv. urography (IVU) Largely replaced by CT and MRI X-ray detects calcification X-ray detects ~60 % of stones detectable with CT IVU visualizes stones as filling absence Nephrocalcinosis

33 Renal CT scan Indications: - renal mass - retroperitoneal mass - ureterolithiasis - acute pyelonephritis parencyhmal involvement (abscess?) - renal artery stenosis (CT angiography) - localisation of an ectopic kidney Limitations: CT contrast material should NOT be given: allergy severe renal impairment (GFR < 30 ml/min/1.73m 2 )

34 Renal CT scan Acute pyelonephritis, multiple abscesses Hypernephroma

35 Renal MRI Indications: - Usually not first-line investigation - non-calculosus urinary obstruction (MR urography) - renal artery stenosis (MR angiography) Limitations: MR contrast material should NOT be given: - Severe renal impairment (GFR < 30 ml/min/1.73m 2 ), increased risk of nephrogenic systemic fibrosis Normal kidneys

36 Renal angiography Indication: - renal artery stenosis / fibromuscular dysplasia - medium- / large-vessel vasculitis - intervention (angioplasty, stent implantation) Renal artery stenosis after angioplasty

37 Renal scintigraphy Indications: - studying renal blood flow and function - functional relevance of renal artery stenosis Radionuclides: 99 Tc-MAG3 (merkapto-acetil-triglicin) : tubular secretion 99 Tc-DTPA (dietilene-triamin-penta-acetat): glomerular filtration 99 Tc-DMSA (dimercaptosuccinat): tubular retention

38 Renal biopsy Indications: isolated, 1-2 g/day proteinuria (with decreasing GFR / increasing proteinuria) nephrotic syndrome ( NOT in children with minimal change disease) acute glomerulonephritis syndrome rapidly progressing glomerulonephritis syndrome (RPGN) acute kidney failure (after exclusion of acute tubular necrosis, pre- and postrenal causes and renal function does not improve after 2 weeks) renal failure of unknown origin (except ultrasound showing bilateral small kidneys) transplant kidney dysfunction

39 Renal biopsy Contraindications: solitary kidney multiple renal cysts renal tumor acute pyelonephritis Uncontrolled bleeding disorder stop ASA 5 days prior PLT < 100 x 10 9 /l Uncontrolled hypertension BP > 160/95 Hgmm

40 Renal biopsy

41 Renal biopsy

42 Evaluation of renal tissue - immunfluorescence Linear pattern Granular pattern Pauci-immun pattern

43 Evaluation of renal tissue light microscopy Normal glomerulus Crescent formation Membranous nephropathy

44 Evaluation of renal tissue electron microscopy Normal glomerulus Fusion of podocyte foot processes (MCD) Membranous nephropathy

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