Urinary syndromes MUDR. IVAN ŘIHÁČEK, PH.D. Introduction Kidney anatomy Differential diagnosis of kidney disease Kidney examination Urine examination Urinary syndromes Diagram of urinary syndromes Anatomy The nephron consists of glomerulus (with afferent and efferent arteriole, Bowmans capsule), proximal tubule, loop of Henle, distal tubule and collecting tubule. Functions of the kidneys Excretion of ammonium, urea and creatinine (products from protein metabolism) Excretion of uric acid (products from nuclei acids) Regulate the body fluid volume and concentration of minerales ◦Sodium, Potasium, Chloride, Calcium, Phosphorus, Magnesium ◦Under control of many hormonal and haemodynamics signals (RAAS, ADH, volumoreceptors…) Regulate the acid-base balance (HCO3- , H+ ) The kidneys are main source of some hormone (volume and metabolic effect) ◦Renin, erytropoetin, calcitriol – vit D3 Signs of renal disease Early signs: Albuminuria: ≥ 30 mg/24h A2 or albumin/creatinine ratio ≥ 3,0 mg/mmol Mild decrease of eGFR: CKD G2 and G3a Advanced signs: Proteinuria: ≥ 300 mg/24h A3 Oliguria and elevated plasma creatinine Hypalbuminemia ˂ 35 g/l Edema Oliguria ˂ 500ml/24h urine Anuria: 0-100ml/24h urine Investigation of renal and urinary tract disease Personal history Physical examination Laboratory work up (creatinine, eGFR, potasium, albumin, imunology) Noninvasive imaging techniques (ultrasound, IVU, pyelography, CT, MRI, radionuclide) Invasive techniques (cystoscopy, pelvi-ureteroscopy, angiography, renal biopsy) Urinanalysis Physical examination Palpation: Bimanual palpation (Israeli's touch) Healthy kidney is not palpable Physical examination Palpation: Ureteral points Pain during renal colic Physical examination Percussion: Tapottement Pain in inflammation Some imaging techniques Endoscopic view of urinary tract Ultrasonography Some imaging techniques Some imaging techniques Dimercaptosuccinic acid labeled by 99mTc DMSA renogram Retrograde pyelography Renal biopsy Obtaining a tissue sample - examination microscopically, histological conclusion = subsequent treatment It is performed with a needle under sonographic control There must be normal blood pressure and blood coagulation testing, monitoring 24h in the hospital Indication: ◦Suspected of rapidly-progressing glomerulonephritis (GN) ◦Proteinuria and hematuria of unclear origin ◦Nephrotic syndrome of unclear cause ◦Acute renal failure of unclear cause ◦Suspected kidney disease in systemic diseases ◦Rapid worsening of renal failure in treated glomerulopathy ◦Suspected kidney transplant rejection Differential diagnosis of acute kidney injury (AKI) Pre-renal Decrease of intravacular volume (hypotension) (fluid) Renal artery stenosis Heart failure (diuretics) Renal Renal parenchymal disease (nefrological care) Post-renal Obstruction (urological care) Differential diagnosis of chronic kidney disease (CKD) Pre-renal Hypertension aterosclerotic disease (large artery) Renal Glomerular disorders (core, GN, diabetic nephropathy, hypertension – small arteries) Interstitial disorders (medulla, tubuli, renal pelvis) Post-renal Obstruction (urological care, renal calculi, tumours, prostate enlargement, infection) Urine examination Preparation: Disinfection around the urethra Medium urine flow Catheterized urine (females) Morning urine (more concentrated) Collected urine for 3, 10, 24 hours Urine chemically: (paper, instrument) PH Glycaemia Proteins Hemoglobine Bilirubine Urobilinogene Ketones Urine examination Urinary sediment: Addis (10 hours night urine) ◦Erytrocyte 1-2 mil/24h ◦Leukocyte 1-4 mil/24h ◦Casts 100 000/24h Hamburger (3 hours urine) ◦Erytrocyte 2000/min ◦Leukocyte 4000/min ◦Casts 60-70/min ◦ Microscopic examination Hematuria (blood in urine) Leukocyturia (white blood cells, inflammation) Cylinders (castings of precipitate from canals) Crystals (depends on PH urine, stones) Microbiological examination of urine Sampling of morning urine Careful disinfection of the external orifice of the urethra Medium current flow/catheterized urine At room temperature as soon as possible send for culture examination Culture media, bacterial type/antibiotic sensitivity, up to 24 hours, ˃ 105 bacteria The most common pathogens: E coli, enterobacter, klebsiela Syndromes Leukocyturia Proteinuria Hematuria Leukocyturia Presence of white blood cells in urine ◦ ◦Urinary tract infections (UTI) ◦women ◦the elderly ◦diabetes ◦pregnancy ◦stones ◦Pus in urine (pyuria, turbid urine = bacterial inflammation) Sterile urine leukocyturia (culture negative) ◦ ◦Gonorrhea ◦Trichomonas, TBC, fungi, mycoplasmas, chlamydia ◦Tubulointerstitial nephropathy ◦Prostate or bladder cancer ◦Injury of urethra ◦Urinary stones, vesicoureteral reflux ◦ ◦ Proteinuria Urine protein quantitatively: Albuminuria (30-300mg/24h) Proteinuria (over 300mg/24h) Small up to 1.5 g/24h Medium 1,5 to 3.5 g/24h Big above 3.5 g/24h Selective: mainly albumin Non-selective: globulins, fibrinogen Urine protein according to origin: Renal ◦Glomerular (diseases of the ball) ◦Tubular (canal diseases) Prerenal (increased serum protein concentrations – paraprotein, Bence-Jones) Postrenal (tumors, urinary tract inflammation, heart failure) Differential dg of proteinuria Hematuria Microscopic: (It does not change the color of the urine) Phase contrast (GN x urinary tract) Glomerulonephritis (+ protein, cylinders) Urinary stones, tumors Infections (+ leukocytes + bacteria) Interstitial nephritis Infectious diseases other than kidneys After extreme physical stress Macroscopic: (Changes color, 1 ml or more of blood/liter of urine) False (porphyry, beetroot, rifampicin !!) ◦ ◦Urinary stones ◦Tumors ◦Trauma ◦TBC (+ leukocyturia without bacteria) ◦Kidney cysts ◦Cystitis, infection ◦Clotting disorder (blood diseases) Going through glomerulus Hematuria Phase contrast erytrocytes Left: normal erytrocytes from urine tract Right: damaged erythrocytes after passing through the glomerulus - GN Differential dg of hematuria Urinary syndromes 1. Small isolated proteinuria 2. Small isolated hematuria 3. Big isolated selective proteinuria 4. Big non-selective proteinuria 5. Proportional proteinuria and hematuria 6. Macroscopic hematuria 1. Small isolated proteinuria Amount of protein up to 2g/24h. It can be intermittent (stress, orthostatic) or permanent. It is typical for: Diabetic nephropathy, early stage Congestive heart failure, Benign nephrosclerosis, Remission glomerulonephritis, Hypertensive renal disease. 2. Small isolated hematuria Microscopic hematuria and proteinuria ≤ 300mg/24 hr. It is typical for: IgA - nephropathy Vasculitis Alport's syndrome Thin basal membrane nephropathy 3. Big isolated selective proteinuria Proteinuria ˃ 5g/24h Erythrocytes are not present or only in negligible quantities. It is clearly diagnostic for minimal glomerular changes in Nephrotic syndrome. 4. Big non-selective proteinuria Proteinuria ˃ 5g/24h and mild hematuria It is typical for: membranous and membranoproliferative glomerulonephritis (GN) diabetic nephropathy amyloidosis focal segmental glomerulosclerosis as part of Nephrotic syndrome. 5. Proportional proteinuria and hematuria Membranoproliferative and mesangioproliferative GN 3 types according to proteinuria and erythrocyturia: • Smal proteinuria ≤ 2g/24 hours with microscopic hematuria • Medium proteinuria 2-5 g/24 h, micro- to macroscopic hematuria • Big proteinuria ˃ 5g / 24 hours with macroscopic hematuria 6. Macroscopic hematuria Macroscopic hematuria with mild proteinuria <1.5g/24h In some acute intestinal or respiratory diseases In IgA-nephropathy In thin basal membrane nephropathy Clinical syndromes Combination of extrarenal symptoms, urinary findings, severity of the renal disorder and rate its progression. Clinical syndromes Syndrome Diagnostic symptoms Clinical symptoms Asymptomatic urine abnormality Small proteinuria, hematuria, sterile pyuria Acute nefritic syndrome (GN) Proteinuria, hematuria, leukocyturia, cylinders, damaged erytrocytes Edema, hypertension, oliguria, azotemia, Acute kidney injury (AKI) Increase of plasma urea, creatinine, oligo/anuria Edema, hypertension, proteinuria, hematuria, pyuria Chronic kidney disease (CKD) Azotemia more than 3 months, anemia, phosphates Hypertension, proteinuria, edema hematuria, polyuria, nycturia Nefrotic syndrome Proteinuria ˃ 3,5g/d, dyslipidemia, hypalbuminemia Edema Urinary tract obstruction Hydronephrosis, urinary retention, oliguria, anuria, azotemia Dysuria, hematuria, pyuria Urinary tract infection (UTI) Bacteriuria ˃ 105 , pyuria, CRP, polakisuria Febrilie, smal proteinuria, hematuria, azotemia Renal tubular syndromes Electrolyt disorders, metabolic acidosis, polyuria Tubular proteinuria, hematuria Uremic syndrome Azotemia ˃ 3M, dyspeptic disorders, multiorgan disorders, Kussmauls breathing, prutitus Edema, hypertension, anemia Renal stones Renal colic, hydronephrosis Hematuria, pyuria Clinical conclusions The standard is the examination of urine and urinary sediment ◦Elementary with paper stick, if positive quantitatively ◦Morning urine sample ◦ When finding erythrocytes and proteins we think of glomerulopathy ◦Phase contrast microscopy and quantitative examination When leukocytes and bacteria are found - UTI ◦Bacteriuria itself is often a contamination