Basics of Nephrology PDF

Basics of nephrology By Dr. Haitham Nabeel Your Date Here Your Footer Here  Introduction to nephrology Your Date Here Your Footer Here Renal anatomy Your Date Here Your Footer Here 3 Re...

Basics of nephrology By Dr. Haitham Nabeel Your Date Here Your Footer Here  Introduction to nephrology Your Date Here Your Footer Here Renal anatomy Your Date Here Your Footer Here 3 Renal anatomy Your Date Here Your Footer Here 4 Arterial system Your Date Here Your Footer Here 5 Glomerular blood flow Your Date Here Your Footer Here 6 Special Kidney Features Right kidney slightly smaller Less development in utero due to liver Left kidney has longer renal vein Often taken for transplant Dead/dying kidney usually not removed in transplant New kidney attached to iliac artery/vein Your Footer Here 7 Kidney functions Excretion of many metabolic breakdown products drugs and toxins. Regulate fluid and electrolyte balance. Regulate blood pressure Regulate acid–base balance In addition, the kidneys activate vitamin D and control the synthesis of red blood cells by producing erythropoietin. Your Date Here Your Footer Here 8 Kidney functions Your Date Here Your Footer Here 9 Nephrons Your Date Here Your Footer Here 10 Renal Corpuscle Your Date Here Your Footer Here 11 Renal Tubule Your Date Here Your Footer Here 12 Renal Tubule Your Date Here Your Footer Here 13  Renal hormones Your Date Here Your Footer Here Renal Hormones Released by kidney Erythropoietin Renin (enzyme) 1,25 Vitamin D Act on kidney Angiotensin II Atrial Natriuretic Peptide (ANP) Antidiuretic hormone (ADH) Aldosterone Parathyroid hormone (PTH) Your Date Here Your Footer Here 15 JG Apparatus JG Cells Modified smooth muscle of afferent arteriole Macula densa Part of distal convoluted tubule JG cells secrete renin Your Date Here Your Footer Here 16 Glomerulus Your Date Here Your Footer Here 17 RAAS Renin-Angiotensin-Aldosterone System Your Date Here Your Footer Here 18 Stimulation Renin Release 1.Low perfusion pressure Low blood pressure or low circulating volume Sensed by afferent arteriole→ JG cell renin release 2.Low NaCl delivery Sensed by macula densa→ JG cell renin release Also constricts afferent arteriole: “tubuloglomerular feedback” 3.Sympathetic activation β1 receptors Also constricts (α) afferent/efferent arterioles Decreases GFR to limit sodium/water excretion Your Date Here Your Footer Here 19 RAAS Renin Converts angiotensinogen to angiotensin I Angiotensin II Multiple effects Aldosterone Collecting duct effects Resorption of Na Excretion of K, H+ Your Date Here Your Footer Here 20 Angiotensin II Efferent arteriole constriction ↓ RPF ↑ GFR Less renal blood flow More Na/H2O filtration Your Date Here Your Footer Here 21 Renal haemodynamics and autoregulation of glomerular filtration rate (GFR). It is evident from this figure how angiotensinconverting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) may be associated with profound drops in GFR in the context of bilateral renal artery stenosis or intravascular volume depletion (which decrease perfusion to afferent arterioles). (NSAIDs = non-steroidal anti-inflammatory drugs) Your Date Here Your Footer Here 22 Angiotensin II Increased Na/H2O reabsorption Several mechanisms Increased proximal tubule resorption via capillary effect Direct proximal tubule resorption through Na/H+ exchange Stimulates aldosterone release Your Date Here Your Footer Here 23 Aldosterone Synthesized/released by adrenal cortex Zona glomerulosa cells Freely crosses cell membrane (steroid) Binds to cytosolic protein receptor Activated receptor modifies gene expression Your Date Here Your Footer Here 24 Aldosterone Increases Na/K-ATPase proteins Increases Na channels (ENaC) of principal cells Promotes K secretion principal cells Promotes H+ secretion intercalated cells Your Date Here Your Footer Here 25 Aldosterone Your Date Here Your Footer Here 26 Aldosterone Overall effect: ↑ sodium/water resorption (↑effective circulating volume) ↑ K excretion ↑H+ excretion Release stimulated by: Angiotensin II High potassium ACTH (minor effect) Your Date Here Your Footer Here 27 Renin-angiotensin- aldosterone system Flowchart summarizing the biochemical and physiological effects of the renin-angiotensin- aldosterone system. Your Date Here Your Footer Here 28 RAAS Drugs ACE-inhibitors Block conversion AI to AII Lower blood pressure Angiotensin receptor blockers (ARBs) Block effects of angiotensin II Lower blood pressure Your Date Here Your Footer Here 29 RAAS Drugs Aldosterone antagonists Spironolactone, eplerenone Lower blood pressure Will ↑K, ↑H+ (↓pH) Potassium-sparing diuretics Triamterene/amiloride Inhibit ENaC Your Date Here Your Footer Here 30 Parathyroid Hormone Maintains calcium levels Released by chief cells of parathyroid gland Main stimulus is ↓[Ca2+] Net Effects: ↑[Ca 2+] plasma ↓ [P043-] plasma ↑ [P043-] urine Your Date Here Your Footer Here 31 Parathyroid Hormone Effects Kidney: ↑ Ca 2+ resorption (DCT) ↓ P043-resorption (PCT) ↑1 ,25-(0H)2 vitamin D production Also has effects on GI tract and bone Your Date Here Your Footer Here 32 Parathyroid Hormone Your Date Here Your Footer Here 33 Vitamin D and the Kidney Proximal Tubule converts vitamin D to active form Your Date Here Your Footer Here 34 EPO Erythropoietin Stimulates red blood cell production in bone marrow Made by interstitial cells peritubular capillary Released in response to hypoxia Decreased production in renal failure Normocytic anemia Your Date Here Your Footer Here 35  Glomerular Filtration Rate Your Date Here Your Footer Here Definition The glomerular filtration rate (GFR) is the sum of the ultrafiltration rates from plasma into the Bowman’s space in each nephron and is a measure of renal excretory function. It is proportionate to body size and the reference value is usually expressed after correction for body surface area as 120 ± 25 mL/min/1.73 m2. Your Date Here Your Footer Here 37 Measurement of GFR The GFR may be measured directly by injecting and measuring the clearance of compounds such as inulin or radiolabelled ethylenediamine-tetra-acetic acid (EDTA), which are completely filtered at the glomerulus and are not secreted or reabsorbed by the renal tubules. This is not performed routinely, however, and is usually reserved for special circumstances, such as the assessment of renal function in potential live kidney donors. Your Date Here Your Footer Here 38 Measurement of GFR Creatinine clearance (CrCl): Minor tubular secretion of creatinine causes CrCl to exaggerate GFR when renal function is poor; can be affected by drugs (e.g. trimethoprim, cimetidine) Needs 24-hr urine collection (inconvenient and often unreliable) Creatinine clearance = (CreaUrine x V) / CreaPlasma ≈GFR Your Date Here Your Footer Here 39  The creatinine excretion and, therefore, the creatinine concentration in the urine varies throughout the day. Urine collected over a 24- hour period allows for a more accurate measurement. However, this method is time-consuming and prone to inaccuracy. That’s why! Your Date Here Your Footer Here 40  Inulin clearance and creatinine clearance (with 24-hour urine collection): allow for the most accurate calculation of the glomerular filtration rate Clinical pearl! Your Date Here Your Footer Here 41 Measurement of GFR Instead, GFR is usually assessed indirectly in clinical practice by measuring serum levels of endogenously produced compounds that are excreted by the kidney. The most widely used is serum creatinine, which is produced by muscle at a constant rate, is almost completely filtered at the glomerulus, and is not reabsorbed. Although creatinine is secreted to a small degree by the proximal tubule, this is only usually significant in terms of GFR estimation in severe renal impairment, where it accounts for a larger proportion of the creatinine excreted. Accordingly, provided muscle mass remains constant, changes in serum creatinine concentrations closely reflect changes in GFR. Your Date Here Your Footer Here 42 Measurement of GFR The relationship between serum creatinine and GFR is not linear, however, and a modest elevation in serum creatinine above the normal range may therefore reflect a substantial decline in GFR. For this reason, several methods have been developed to estimate GFR from serum creatinine measurements but the most widely used is the Modification of Diet in Renal Disease (MDRD) equation. Your Date Here Your Footer Here 43  Serum creatinine levels do not start rising until the GFR is reduced by approx. 50%. Clinical pearl! Your Date Here Your Footer Here 44 Serum creatinine and the glomerular filtration rate (GFR). The relationship between serum creatinine and estimated GFR (eGFR) is non-linear; small increases above the normal range (e.g. 80–100 μmol/L; green lines) can therefore indicate a substantial decline in renal function (e.g. 105–80 mL/min/1.73 m2; conversely, in the high range, large changes in creatinine (e.g. 400–600 μmol/L; blue lines) can occur with only small declines in renal function (e.g. 20–15 mL/ min/1.73m2). Your Date Here Your Footer Here 45 Serum creatinine and the glomerular filtration rate (GFR). Creatinine is dependent on muscle mass; the same creatinine value may therefore reflect very different levels of renal function depending on the age and sex of the individual. To convert creatinine in mg/dL to μmol/L, multiply by 88.4. Your Date Here Your Footer Here 46 eGFR by MDRD This equation is dependent on 4 variables: 1-Age 2-Sex 3-Ethnicity 4-serum creatinine Link for iOS: https://apps.apple.com/iq/app/gfr- calculator-mdrd-ckd/id523479289?l=ar Link for android: https://play.google.com/store/apps/details?i d=co.mdapp.gfr Your Date Here Your Footer Here 47  The MDRD formula is based on the serum creatinine value and so is heavily influenced by muscle mass; eGFR may therefore be misleading in individuals whose muscle bulk is outside the normal range for their sex and age. Clinical pearl! Your Date Here Your Footer Here 48 Limitations of MDRD It is only an estimate, with wide confidence intervals (90% of patients will have eGFR within 30% of their measured GFR, and 98% within 50%) It is based on serum creatinine, and so may over-estimate actual GFR in patients with low muscle mass (e.g. those with cachexia, amputees) and under-estimate actual GFR in individuals taking creatine supplements (creatinine is a metabolite of creatine) or trimethoprim (inhibits secretion of creatinine) Creatinine level must be stable over days; eGFR is not valid in assessing acute kidney injury It tends to under-estimate normal or near-normal function, so slightly low values should not be over-interpreted Your Date Here Your Footer Here 49 Limitations of MDRD In the elderly, who constitute the majority of those with low eGFR, there is controversy about categorising people as having chronic kidney disease on the basis of eGFR alone, particularly at stage 3A, since there is little evidence of adverse outcomes when eGFR is > 45 mL/min/1.73 m2 unless there is also proteinuria eGFR is not valid in under-18s or during pregnancy Ethnicity is not taken into account in routine laboratory reporting; the laboratory eGFR value should therefore be multiplied by 1.21 for black people. Your Date Here Your Footer Here 50 Stages of CKD Your Date Here Your Footer Here 51  Few patients will understand eGFR in terms of mL/min/1.73 m2; it may therefore be helpful to assume that a GFR of 100 mL/ min/1.73 m2 is approximately normal and to discuss eGFR values in terms of a percentage of normal, e.g. 25 mL/min/1.73 m2 = 25% of normal kidney function. Practical tip! Your Date Here Your Footer Here 52 Why to measure GFR? Staging Prognosis Intervention for prevention Hold progression Drug dose calculation Your Date Here Your Footer Here 53  Urine Investigations Your Date Here Your Footer Here Urinalysis A urinalysis is a commonly ordered panel of tests on a urine sample which can evaluate: Renal failure UTI Stone disease GU malignancy Acid base disorders Volume status Rhabdomyolsis Your Date Here Your Footer Here 55 Urinalysis Gross inspection Dipstick Microscopy Volume Specific gravity WBCs Color pH RBCs Turbidity Glucose Bacteria Heme Crystals Protein Casts Leucocyte esterase Nitrites Ketones BilirubinUrobilinogen Your Date Here Your Footer Here 56 Volume Normally 1.5–2.5 L / Day. Oliguria is defined as being present when less than 400 mL of urine is passed per day. Anuria is deemed to exist when less than 100 mL of urine is passed per day Your Date Here Your Footer Here 57  Urine volume alone is a poor indicator of the severity of kidney disease Clinical pearl! Your Date Here Your Footer Here 58 Color Urine color is influenced by hydration. Urine color is also influenced by medial conditions, medications and ingested foods. Your Date Here Your Footer Here 59 Color 60 Turbidity Turbid may indicate the presence of a UTI or precipitated crystals. However, it is not a specific finding for either of these conditions (i.e. one should not assume the presence of a UTI based on turbid urine) Your Date Here Your Footer Here 61 Dipstick A urine dipstick consists of a series of pads embedded on a reagent strip that provides a quick, semi quantitative assessment of various potential contents of urine. Your Date Here Your Footer Here 62 Specific gravity The urine specific gravity can vary from 1.001 to 1.035 depending upon renal perfusion and volume status. Under normal conditions (euvolemia and normal renal perfusion) the specific gravity is close to 1.010 Your Date Here Your Footer Here 64 Specific gravity SG close to 1.001 SG fixed at 1.010 SG close to 1.035 Excessive hydration Advanced kidney failure Dehydration Diabetes inspidus SIADH ATN CHF Cirrhosis Glycosuria Proteinuria Recent IV contrast Your Date Here Your Footer Here 65 pH Depending on physiological state, the kidneys can produce urine with a pH ranging from 4.5 to 8.0 When the kidneys are functioning normally, they will excrete more H+ in acidemia (resulting in lower pH), and excrete less H+ in alkalemia (resulting in higher pH) Situation in which checking urine pH is particularly helpful: Diagnosing a RTA Monitoring urine alkalinization to prevent precepitation of myoglobin in rhabdomyolysis and toaid the eliminaton of certain drugs (e.g. aspirin, methotrexate) Differentiation between different types of kidney stones Your Date Here Your Footer Here 66 pH ↓pH ↑pH Acidemia Alkalemia Distal RTA The urine pH is highly dependent UTI secondary to on diet, and cannot be used to infer urease- producing anything about the acid-base status organisims (e.g. of a patient in the absence of an proteus, kebsiella) ABG and metabolic panel Your Date Here Your Footer Here 67 Glucose Glucose is freely filtered through the glomerulus bit almost all is reabsorbed in the proximal tubule. Glucose in urine is referred to as glycosuria If severe, glycosuria can lead to an osmotic duresis and dehydration. Detectable glucose Hyperglycemia Proximal tubular dysfunction (e.g. Your Date Here fanconi syndrome) Your Footer Here 68 Heme Urine dipstick for heme is highy sensitive for hemoglobin However, it also detects myoglobin Your Date Here Your Footer Here 69  A urine dipstick cannot differentiate between hematuria, hemoglobinuria, or myoglobinuria. Therefore, every positive test result for heme must be confirmed with the presence of RBCs on microscopy. Clinical pearl! Your Date Here Your Footer Here 70 Protein Detection of protein on urine dipstick is most sensitive for albumin. It does not typically detects immunogloin light chains. Sensitivity is highly dependent on urine concentration (the more concentrated. the more sensitive) Detectable protein Glomerular diseases Over flow proteinuria Your Date Here Post-renal proteinuria Your Footer Here 71 Protein Semi quantitative measurement of urine albumin, which is expressed on a scale from 0 to +++ or ++++. Number of (+) in dipstick Approximate amount of protein + 800 mg/l ++ 1450 mg/l +++ 3000 mg/l Your Date Here Your Footer Here 72  Normal and microalbuminuria are not detected by dipstick! Clinical pearl! Your Date Here Your Footer Here 73 Leukocyte esterase and nitrites Leukocyte esterase and nitrites are used to aid in the diagnosis of UTIs. Leukocyte esterase is an enzyme released by WBCs and is used as a qualitative measure of WBCs in the urinary tract. Nitrites detect the presence of Enterobaceriacae, which convert nitrates to nitrites. Your Date Here Your Footer Here 74 Leukocyte esterase and nitrites Your Date Here Your Footer Here 75 Ketones Ketonuria Ketoacidosis Diabetes Alcohol Starvation Your Date Here Your Footer Here 76 Bilirubin and urobilinogen Your Date Here Your Footer Here 77 Bilirubin and urobilinogen Your Date Here Your Footer Here 78 The following parameters are normally not present in urine:- Glucose: (glucosurea), Protein: (proteinurea or albuminurea) Blood: (hematureaor hemoglobinurea) Bile salts: in patients with jaundice. Ketone bodies or Acetone: could appear in urine in late stages of diabetes mellitus Your Date Here Your Footer Here 79 Urinalysis Gross inspection Dipstick Microscopy Volume Specific gravity WBCs Color pH RBCs Turbidity Glucose Bacteria Heme Crystals Protein Casts Leucocyte esterase Nitrites Ketones BilirubinUrobilinogen Your Date Here Your Footer Here 80 RBCs RBCs are quantified as # of cells/ “high power field”. ≥3 RBCs/HPF should be considered abnormal Presence of dysmorphic RBCs is strongly suggestive of glomerular Microscopic Hematuria disease. Your Date Here Your Footer Here 81 Acanthocytes Photomicrograph of a peripheral blood smear (Wright-Giemsa stain) Numerous red blood cells are present. Some of them have irregular protrusions at the surface. This is a typical finding of acanthocytes. Your Date Here Your Footer Here 82 RBCs RBCs are quantified as # of cells/ ↑RBC UTI “high power field”. Renal stone GU malignancy ≥3 RBCs/HPF should be considered Recent instrumentation Coagulopathy abnormal Glomerulonephritis Sickle cell anemia Presence of dysmorphic RBCs is Renal tuberculosis strongly suggestive of glomerular Vigorous exercise Contamination with disease. menstrual blood Your Date Here Your Footer Here 83 WBCs ↑WBC WBCs are quantified as # of cells/ UTI “high power field”. Indwelling urinary catheter >5 RBCs/HPF should be considered GU malignancy abnormal Recent instrumentation Chronic interstitial nephritis Interstitial cystitis Intra-abdominal inflammatory process adjacent to the GU tract Contamination with vaginal secretions Your Date Here Your Footer Here 84 Bacteria Bacteria are a common finding on urine microscopy and are consistent with a UTI. However, in the absence of symptoms, particularly if leucocyte esterase and nitrites are negative, it is probably due to poor collection technique. Your Date Here Your Footer Here 85 Use of the UA to diagnose a UTI There are no standarized approaches on how to do this. The presence of nitrites is the most specific finding and has the highest positive predictive value. However, leukocyte esterase, WBCs and even bacteria on microscopic exam are not specific and their presence does not necessarily indicate infection. Diagnosis of a UTI needs also to consider the presence of symptoms and a positive urine culture (if one is done, which is probably not necessary in young, otherwise healthy women with typical symptoms) Your Date Here Your Footer Here 86 Crystals Crystals are highly organized, microscopic solids usualld composed of a small number of different ions and/or molecules. Formation of crystals is most dependent upon: Concentration of ions and molecules Urine pH Small amounts of most types of crystals are not necessarily pathologic. Your Date Here Your Footer Here 87 Crystals Your Date Here Your Footer Here 88 Casts Casts are lond, cyidrecal structures formed in the renal tubules sue to precepitation of Tamm-Horsfall mucoprotein. Cast formation is promoted by acidic and/or concentrated urine Casts are described based on the elements embedded within the mucoprotein matrix Hyaline casts seen in Presence of casts can provide important tubules on renal biopsy insights into etiologies of AKI. Your Date Here Your Footer Here 91 Red blood cell cast Photomicrograph of urine sediment (high magnification) A cast consisting of multiple red blood cells is visible. RBC casts are typically seen in patients with glomerular damage (e.g., glomerulonephritis). Your Date Here Your Footer Here 92 Casts Your Date Here Your Footer Here 93 Further laboratory tests Urine osmolality Can be used to evaluate urine concentration More accurate than the dipstick measurement for specific gravity Urine osmolar gap (UOG): The difference between measured urine osmolality and calculated urine osmolality, used to estimate urine NH4+ concentration in metabolic acidosis. Urine electrolytes Urine sodium (Na+): e.g., low urine sodium indicates that the kidneys are trying to retain free water by reabsorbing Na+ (e.g., due to dehydration) Fractional excretion of sodium: can help determine the cause of acute kidney injury Urine creatinine: used to calculate creatinine clearance Urine culture Your Date Here Your Footer Here 94 Fractional excretion of sodium (FeNa) Definition: percentage of the glomerular filtered sodium (NaFiltered) that is eventually excreted in the urine (NaExcreted) Usage Can help establish the cause of acute kidney injury Can help distinguish between renal and extrarenal etiology in hypotonic hyponatremia Calculation: FeNa = (NaUrine x CreaPlasma) / (NaPlasmax CreaUrine) Your Date Here Your Footer Here 95 Fractional excretion of sodium (FeNa) Interpretation In acute kidney injury Low FeNa (< 1%): indicates a prerenal cause (renal hypoperfusion) High FeNa (> 2%): indicates an intrarenal etiology (e.g., acute tubular necrosis) Inconclusive FeNa (1–2%): can be seen with either disorder In hypotonic hyponatremia Low FeNa (< 1%): extrarenal cause High FeNa (> 1%): renal cause Your Date Here Your Footer Here 96 Common patterns of UA abnormalities Your Date Here Your Footer Here 97  Blood investigations Your Date Here Your Footer Here Hematology A normochromic normocytic anaemia is common in CKD and is due in part to deficiency of erythropoietin and bone marrow suppression secondary to toxins retained in CKD. Iron deficiency from urinary tract bleeding Haemolytic anaemia secondary to disorders such as haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Your Date Here Your Footer Here 99 Hematology Neutrophilia and raised erythrocyte sedimentation rate (ESR) in vasculitis or sepsis. Lymphopenia and raised ESR in systemic lupus erythematosus (SLE). Fragmented red cells on blood film and low platelets may be observed in thrombotic microangiopathies such as HUS/TTP and malignant hypertension. Pancytopenia may occur in SLE or bone marrow suppression due to myeloma. Your Date Here Your Footer Here 100 Biochemistry Abnormalities of routine biochemistry are common in renal disease. Your Date Here Your Footer Here 101 Creatinine Normal value: 60 -120 Umol/l (/88.4) = 0.68 –1.36 mg/dl Indirect indicator of renal function Creatinine is a metabolite of creatine in the muscle (creatine + ATP ⇄ phosphocreatine + ADP). Creatinine is entirely removed by glomerular filtration. Because creatinine is produced at a relatively constant rate and freely filtered by the glomeruli, it can be used to estimate GFR. Your Date Here Your Footer Here 102 Serum cystatin C A more precise indicator of the GFR than serum creatinine Cystatin C is a small protein that inhibits cysteine proteinases and is produced by all nucleated cells. Analysis is more complex and expensive; therefore, not routinely ordered. Your Date Here Your Footer Here 103 Urea Normal values: 2.5 –6.6 mmol/l ( x 6 ) = 15-40 mg/dl Serum levels of urea are often increased in kidney disease but this analyte has limited value as a measure of GFR since levels increase with protein intake, following gastrointestinal haemorrhage and in catabolic states. Urea levels may be reduced in patients with chronic liver disease or anorexia and in malnourished patients, independently of changes in renal function. Your Date Here Your Footer Here 104 Urea Increased Urea Decreased Urea High production low production High protein intake liver failure GIT haemorrhage Anorexia Catabolic states ( infection ,fever, surgery, Malnutrition trauma &Cancer ) Corticosteroid & Tetracyclines Low elimination (KIDNEY DISEASE) low elimination Glomerular disease Elevated glomerular filtration rate, e.g. Reduced renal blood flow pregnancy Hypotension Urinary obstruction Tubulointerstitial nephritis Dehydration 105 BUN:Creat ratio Can help diagnose the underlying cause in acute kidney injury 10:1–20:1 can be normal or may indicate a postrenal cause. ≥ 20:1 indicates prerenal cause: Urea reabsorption is increased, which is typical in patients with dehydration or hypoperfusion. ≤ 15:1 indicates intrarenal cause: Renal damage causes decreased urea reabsorption. Your Date Here Your Footer Here 106 Calcium, phosphate and PTH Serum calcium tends to be reduced and phosphate increased in CKD, in association with high parathyroid hormone (PTH) levels caused by reduced production of 1,25-dihydroxyvitamin D (1,25(OH)2D) by the kidney (secondary hyperparathyroidism). In some patients, this may be accompanied by raised serum alkaline phosphatase levels, which are indicative of renal osteodystrophy. Your Date Here Your Footer Here 107 Miscellaneous Serum bicarbonate may be low in renal failure and in renal tubular acidosis. Serum albumin may be low in liver disease, as a negative acute phase response or due to malnutrition/malabsorption, but if it is a new finding it should prompt urinalysis to exclude nephrotic syndrome. Your Date Here Your Footer Here 108 Immunology Antinuclear antibodies, antibodies to extractable nuclear antigens and anti-double-stranded DNA antibodies may be detected in patients with renal disease secondary to SLE. Antineutrophil cytoplasmic antibodies (ANCAs) may be detected in patients with glomerulonephritis secondary to systemic vasculitis. Antibodies to GBM in patients with Goodpasture’s syndrome and low levels of complement may be observed in a number of kidney diseases Your Date Here Your Footer Here 109 Renal biopsy Why to do kidney biopsy? Establish the diagnosis. Severity of renal disease Judge the prognosis Need for treatment Your Date Here Your Footer Here 110 Renal biopsy: Indications Acute kidney injury and chronic kidney disease of uncertain aetiology Nephrotic syndrome or glomerular proteinuria (protein:creatinine ratio > 100 mg/mol) in adults Nephrotic syndrome in children that has atypical features or is not responding to treatment Nephritic syndrome Renal transplant dysfunction Rarely performed for isolated haematuria or isolated low-grade proteinuria in the absence of impaired renal function or evidence of a multisystem disorder Your Date Here Your Footer Here 111 Renal biopsy: Contrandications Disordered coagulation or thrombocytopenia. Aspirin and other antiplatelet agents increase bleeding risk Uncontrolled hypertension Kidneys < 60% predicted size Solitary kidney* (except transplants) Your Date Here Your Footer Here 112 Renal biopsy: Complications Pain, usually mild Bleeding into urine, usually minor but may produce clot colic and obstruction Bleeding around the kidney, occasionally massive and requiring angiography with intervention, or surgery Arteriovenous fistula, rarely significant clinically Your Date Here Your Footer Here 113 Renal biopsy: procedure The procedure is performed transcutaneously under local anaesthetic with ultrasound or contrast radiography guidance to ensure accurate needle placement into a renal pole. Light microscopy, electron microscopy and immunohistological assessment of the specimen may all be required. Your Date Here Your Footer Here 114 Procedure Your Date Here Your Footer Here 115  Imaging in Nephrology Your Date Here Your Footer Here Ultrasound Renal ultrasound is a valuable non-invasive technique that may be performed to assess renal size and to investigate patients who are suspected of having obstruction of the urinary tract, renal tumours, cysts or stones. Ultrasound can also be used to provide images of the prostate gland and bladder, and to estimate the completeness of emptying in patients with suspected bladder outflow obstruction. In addition, it can reveal other abdominal, pelvic and retroperitoneal pathology Your Date Here Your Footer Here 117 Normal renal ultrasound Case courtesy of Dr Matthew Lukies, Radiopaedia.org, rID: 50538 Your Date Here Your Footer Here 118 Hydronephrosis Right kidney ultrasound (longitudinal transhepatic view) Ballooning of the renal pelvis has displaced the renal parenchyma. As a result, the renal parenchyma is identifiable only as a narrow margin. These findings indicate grade IV hydronephrosis. Your Date Here Your Footer Here 119 Renal cyst Ultrasound of left kidney There is a thin-walled, anechoic lesion (green overlay) protruding from the renal cortex. There is posterior acoustic enhancement (green hatched overlay) with hypoechoic edge shadow on either side, indicating this lesion is fluid-filled. The renal capsule is demarcated by a green line. These findings are consistent with a renal cyst. K: Kidney; C: Cyst Your Date Here Your Footer Here 120 Ultrasound Ultrasound is important in distinguishing between CKD from AKI. How? Ultrasonography may show increased signal in the renal cortex with loss of distinction between cortex and medulla, which is characteristic of CKD. Your Date Here Your Footer Here 121 US in CKD The kidneys show increased parenchymal echogenicity with altered corticomedullary differentiation. Case courtesy of Dr Fazel Rahman Faizi rID: 67158 Your Date Here Your Footer Here 122 Ultrasound Doppler imaging can be used to study blood flow in extrarenal and larger intrarenal vessels, and to assess the resistivity index (peak systolic velocity − end- diastolic velocity/peak systolic velocity in the intrarenal arteries), which may be elevated (> 0.7) in various diseases, including acute tubular necrosis and rejection of a renal transplant. Your Date Here Your Footer Here 123  Renal ultrasound is operator- dependent and the results are often less clear in obese patients. Clinical pearl! Your Date Here Your Footer Here 124 Computed tomography Computed tomography urography (CTU) is used to evaluate cysts and mass lesions in the kidney or filling defects within the collecting systems. CTU has largely replaced the previous gold-standard investigation of intravenous urography (IVU) for investigation of the upper urinary tract, having the advantage of providing complete staging information and details of surrounding organs. Contrast enhancement is particularly useful for characterising mass lesions within the kidney and differentiating benign from malignant lesions. Your Date Here Your Footer Here 125 CT abdomen CT abdomen (with contrast; axial plane) Normal abdominal CT image at the level of the left renal vein. White arrow: left renal vein. Your Date Here Your Footer Here 126 Renal cell carcinoma Axial CT of the abdomen after oral and IV contrast medium administration A large, relatively sharp demarcated tumor can be seen in the right kidney. The tumor has a central, hypodense necrotic area that is surrounded by solid, capsular regions. This appearance is typical for renal cell carcinoma. Your Date Here Your Footer Here 127 Computed tomography Non-contrast CT of kidneys, ureters and bladder (CTKUB) is the method of choice for demonstrating stones within the kidney or ureter. CT without contrast gives clear definition of retroperitoneal anatomy regardless of obesity and is superior to ultrasound in this respect Your Date Here Your Footer Here 128 Nonobstructive renal calculus CT abdomen (with oral contrast; axial plane) The calcific density in the left renal pelvis is a calculus. There is no dilatation of the renal pelvis to indicate obstruction. Atherosclerotic calcification of the abdominal aorta is seen. Your Date Here Your Footer Here 129 Computed tomography For investigation of patients with renal trauma, a triple-phase CT scan with a delayed phase, to assess the integrity of the collecting system, is performed. Your Date Here Your Footer Here 130  Drawbacks of contrast-enhanced CT scans include the fact that relatively large doses of contrast medium are required, which can cause renal dysfunction, and that the radiation dose is significant Clinical pearl! Your Date Here Your Footer Here 131 Contrast nephrotoxicity Acute deterioration in renal function commencing < 48 hrs after administration of IV radiographic contrast media. Risk factors Pre-existing renal impairment Use of high-osmolality, ionic contrast media and repetitive dosing in short time periods Diabetes mellitus Myeloma Your Date Here Your Footer Here 132 Contrast nephrotoxicity Prevention Provide hydration with free oral fluids plus IV isotonic saline 500 mL, then 250 mL/hr during procedure Avoid nephrotoxic drugs; withhold non-steroidal anti- inflammatory drugs (NSAIDs). Omit metformin for 48 hrs after the procedure, in case renal impairment occurs N-acetylcysteine may provide some protection but data are conflicting If the risks are high, consider alternative methods of imaging Your Date Here Your Footer Here 133 Magnetic resonance imaging Magnetic resonance imaging (MRI) offers excellent resolution and gives good distinction between different tissue types. It is very useful for local staging of prostate, bladder and penile cancers. Magnetic resonance angiography (MRA) provides an alternative to CT for imaging renal vessels but involves administration of gadolinium-based contrast media, which may carry risks for patients with impaired renal function. Whilst MRA gives good images of the main renal vessels, stenosis of small branch arteries may be missed Your Date Here Your Footer Here 134 Nephrogenic sclerosing fibrosis after MRI contrast agents Chronic progressive sclerosis of skin, deeper tissues and other organs, associated with gadolinium-based contrast agents Only reported in patients with renal impairment, typically on dialysis or with GFR < 15 mL/min/1.73 m2, but caution is advised in patients with GFR < 30 mL/min/1.73 m2. Your Date Here Your Footer Here 135 Renal arteriography Renal arteriography involves taking X-rays following an injection of contrast medium directly into the renal artery. The main indication is to investigate renal artery stenosis or haemorrhage following renal trauma. Renal angiography can often be combined with therapeutic balloon dilatation or stenting of the renal artery. It can be used to occlude bleeding vessels and arteriovenous fistulae by the insertion of thin platinum wires (coils). These curl up within the vessel and promote thrombosis, thereby securing haemostasis. Your Date Here Your Footer Here 136 Pyelography Pyelography involves direct injection of contrast medium into the collecting system from above (antegrade) or below (retrograde). It offers the best views of the collecting system and upper tract, and is often used to identify the cause of urinary tract obstruction. Your Date Here Your Footer Here 137 Pyelography Antegrade pyelography requires the insertion of a fine needle into the pelvicalyceal system under ultrasound or radiographic control. In addition to visualising the cause of obstruction, percutaneous nephrostomy drainage can be established and often stents can be passed through any obstruction. Your Date Here Your Footer Here 138 Pyelography Retrograde pyelography can be performed by inserting a ureteric catheter into the ureteric orifice at cystoscopy and again a stent can be inserted to bypass any obstruction. Your Date Here Your Footer Here 139 Retrograde pyelography The best views of the normal collecting system are shown by pyelography. A catheter has been passed into the left renal pelvis at cystoscopy. The anemone-like calyces are sharp-edged and normal. Your Date Here Your Footer Here 140 Radionuclide studies These are functional studies requiring the injection of gamma ray-emitting radiopharmaceuticals that are taken up and excreted by the kidney, a process that can be monitored by an external gamma camera. Your Date Here Your Footer Here 141 Radionuclide studies Dynamic radionuclide studies are performed with mercaptoacetyltriglycine labelled with technetium (99mTc- MAG3), which is filtered by the glomerulus and excreted into the urine. Imaging following 99mTc-MAG3 injection can provide valuable information about the perfusion of each kidney but is not a reliable method for identifying renal artery stenosis. In patients with significant obstruction of the outflow tract, 99mTc-MAG3 persists in the renal pelvis and a loop diuretic fails to accelerate its disappearance. Your Date Here Your Footer Here 142 Radionuclide studies This can be useful in determining the functional significance of an equivocally obstructed collecting system without undertaking pyelography Formal measurements of GFR can be made by radionuclide studies following the injection of diethylenetriamine penta-acetic acid (99mTc-DPTA). Your Date Here Your Footer Here 143 Radionuclide studies Static radionuclide studies are performed with dimercaptosuccinic acid labelled with technetium (99mTc- DMSA), which is taken up by proximal tubular cells. Following intravenous injection, images of the renal cortex are obtained that show the shape, size and relative function of each kidney. This is a sensitive method for demonstrating cortical scarring in reflux nephropathy and a way of assessing the individual function of each kidney. Your Date Here Your Footer Here 144 Radionuclide studies Radionuclide bone scanning following the injection of methylene diphosphonate (99mTc-MDP) is indicated to assess the presence and extent of bone metastases in men with advanced prostate cancer. Your Date Here Your Footer Here 145 DMSA radionuclide scan. A posterior view is shown of normal left kidney and a small right kidney (with evidence of cortical scarring at upper and lower poles) that contributes only 39% of total renal function. Your Date Here Your Footer Here 146 Cholesterol emboli These present with renal impairment, haematuria, proteinuria and sometimes eosinophilia with inflammatory features that can mimic a small-vessel vasculitis. The symptoms are provoked by showers of cholesterol- containing microemboli, arising in atheromatous plaques in major arteries. On clinical examination, signs of large-vessel disease and microvascular occlusion in the lower limbs (ischaemic toes, livedo reticularis) are common but not invariable. There is no specific treatment Your Date Here Your Footer Here 147 Cholesterol emboli The foot of a patient who suffered extensive atheroembolism following coronary artery stenting. Your Date Here Your Footer Here 148  The diagnosis should be suspected when these clinical features occur in patients with widespread atheromatous disease, who have undergone interventions such as surgery or arteriography Clinical pearl! Your Date Here Your Footer Here 149  Presenting problems in Nephrology Your Date Here Your Footer Here  Hematuria Your Date Here Your Footer Here A 23-year-old male comes to the ED because of blood in his urine. 152 Notes in hematuria Healthy individuals may have occasional red blood cells in the urine (up to 12 500 cells/mL), but the presence of visible (macroscopic) haematuria or non-visible haematuria (microscopic, only detectable on dipstick testing) is indicative of significant bleeding from somewhere in the urinary tract. Once infection, menstruation and causes of a positive urinary dipstick in the absence of red cells (haemoglobinuria / myoglobinuria) have been excluded both visible and persistent non-visible haematuria require investigation, as they may be caused by malignancy or indicate glomerulonephritis. Your Date Here Your Footer Here 153 Causes of haematuria Your Date Here Your Footer Here 154 Hematuria Diagnostic Framework Glomerular Non-glomerular Hematuria mimicks Immune complex mediated Non-Glomerular Ureter/Bladd Prostate Unknown Contamination from IgA nephropathy kidney erer/urethra menstrual blood IgA vasculitis Lupus nephritis Rhabdomyolysis Infection-related (myoglobinuria) Pyelonephritis UTI BPH Exercise induced glomerulonephritis Urotheliac hematuria Hemolytic anemia Renal cell cancer (e.g. Prostate Anti-GBM disease (hemoglobinuria) carcinoma bladder cancer Idiopathic cancer) ANCA associated vasculitis Porphyria Polycystic kidney Uretral Polyangitis with disease stones granulomatosis Beet ingestion Uretral Microscopic polyangitis stricture Churg -strauss syndrome Factitious hematuria Hemorrhagic cystitis Genetic disorders Traumatic Thin basement membrane foley disease placement Recent urological procedure 155 Glomerular Vs. Non-Glomerular hematuria Glomerular Non-Glomerular RBCs Morphology Dysmorphic Normal RBCs Casts Sometimes present Absent Clots Absent Sometimes present Proteinuria >500mg/day, mostly albumin 40 then rectal exam Skin exam for signs of autoimmune diseases 158 Visible hematuria Visible haematuria is most likely to be caused by tumour, which can affect any part of the urogenital tract and patients with visible haematuria must therefore be referred to urology for imaging (ultrasound or CT scan) and cystoscopy. Other common causes of visible haematuria are urine infection and stones. Visible haematuria may also be encountered in patients with IgA nephropathy, typically following an upper respiratory tract infection. Your Date Here Your Footer Here 159 Non visible hematuria Non-visible haematuria may also indicate an underlying tumour, and all patients over 40 years old with persistent (detected on at least 2 of 3 consecutive dipstick tests) non- visible haematuria should therefore undergo imaging and cystoscopy. In younger patients, an underlying tumour is much less likely, and if a glomerular cause is not suspected, it may be appropriate to manage them by periodic observation in primary care, although occasionally these individuals develop significant overt renal disease during follow-up. Your Date Here Your Footer Here 160 Glomerular hematuria A characteristic feature of glomerular bleeding is an ‘active urinary sediment’ (the presence of dysmorphic red blood cells or red cell casts on microscopy); this is not always present, however. Patients with visible and non-visible haematuria should also be assessed for hypertension, proteinuria, reduced/declining renal function, family history of renal disease or features of systemic disease. The presence of any of these features raises the possibility of intrinsic renal pathology and warrants referral to nephrology for further investigation, including consideration of renal biopsy. Your Date Here Your Footer Here 161 Approach to hematuria Your Date Here Your Footer Here 162  Edema Your Date Here Your Footer Here  A 58-year-old female woman presents to outpatient clinic complaining of persistent swelling of her feet and ankles. 164 EDEMA Pathophysiology 165 EDEMA Pathophysiology 166 Edema diagnostic framework Increased Decreased oncotic Increased capillary Lymphatic Miscellaneous hydrostatic pressure permeability obstruction pressure Volume expansion Malnutrition Sepsis Malignancy Hypothyroidism Kidney failure * Lymph node dissection Pregnancy Cirrhosis cellulitis * Infltraton of lymphatics Medication side effect* Extrinsic compression of (NSAIDs) Nephrotic syndrome lymphatics Acute salt load Heart failure * Filariasis Venous obstruction /insufficiency Heart failure* Pulmonary HPT Cirrhosis* DVT * *most common causes of acute edema *most common causes of chronic edema Chronic venous stasis * Arteriolar vasodilation Dihydropiridine Ca 167 channel blockers Focused history What Important questions to ask in History? Duration of edema Distribution (legs, arms, both or generalized; symmetric Vs. Asymmetric) Prescence of pain or redness of affected extremities, shortness of breath, abdominal distension, symptoms of hypothyroidism. History of cardiac, pulmonary, liver or renal disease (and relevant risk factors) Medication history Travel to areas in which filariasis is endemic 168 What examination to perform? Vitals Characterization of edema (e.g. distribution, symmetry, extent, severity, pitting Vs. non-pitting and concurrent erythema/warmth/tenderness) Cardiac (including JVP), pulmonary and abdominal exams Skin exam (e.g. signs of chronic venous stasis, signs of liver disease) 169  EDEMA: Can be generalized or localized. Generalized edema is due to: Fluid overload : congestive heart failure, renal failure, iatrogenic. Hypoprotenemia: chronic liver disease, nephrotic syndrome, malabsorption and malnutrition. 170  Localized edema: Venous thrombosis Lymphatic Inflammatory A patient with bilateral leg edema, mention one bedside test to differentiate Congestive heart failure (CHF) from Chronic Liver Disease? JVP examination. 171 172 Clinical findings Dependent areas, such as the ankles and lower legs, are typically affected first but oedema can be restricted to the sacrum in bed- bound patients. With increasing severity, oedema spreads to affect the upper parts of the legs, the genitalia and abdomen. Ascites is common and often an earlier feature in children or young adults, and in liver disease. Pleural effusions are common but frank pulmonary oedema is rare. Facial oedema on waking is common Features of intravascular volume depletion (tachycardia, postural hypotension) may occur when oedema is due to decreased oncotic pressure or increased capillary permeability. Your Date Here Your Footer Here 173 Clinical findings The pitting characteristics of edema reflect the viscosity of the edema fluid, which in turn depends largely on its protein concentration. Edema fluid with low protein levels (e.g., hypoalbuminemia, congestive heart failure) pits easily and recovers relatively quickly compared with edema fluid that has higher protein levels (lymphedema, inflammatory edema). A clue to low-protein edema (i.e., edema associated with a serum albumin level less than 3.5 g/dL) is edema that pits easily with only 1 to 2 seconds of thumb pressure over the tibia, and then, after removal of the thumb, begins to recover within 2 to 3 seconds. 174 Clinical findings Lymphedema is painless, firm edema that characteristically causes squaring of the toes and a dorsal hump on the foot. In contrast to venous edema, lymphedema varies little during the day and ulceration is uncommon unless there is secondary infection. Even though lymphedema has high protein levels, clinical experience reveals that lymphedema does pit early in its course although it eventually becomes nonpitting, hard, and “woody” as secondary fibrosis ensues. 175 Clinical findings Lipedema consists of bilateral deposition of excess subcutaneous fatty tissue in the legs that does not pit with pressure and whose most characteristic feature is sparing of the feet. Lipedema occurs exclusively in obese women. 176 PITTING EDEMA In patients with bilateral pitting edema of the legs, the most important diagnostic finding is the patient’s venous pressure, estimated from examination of the neck veins. If the neck veins are abnormally distended →cardiac disease or pulmonary hypertension is at least partly responsible for the patient’s edema; if they are normal→ another cause is responsible, such as liver disease, nephrosis, chronic venous insufficiency, or one of the patient’s medications. Clinicians’ estimates of venous pressure are accurate, with studies showing that the finding of elevated neck veins predicts an abnormally increased central venous pressure (i.e., >8 cm H2O) with a positive likelihood ratio (LR) of 8.9 177 LYMPHEDEMA Lymphedema is classified as primary (i.e., congenital abnormality of the lymphatic systems) or secondary (damage to the lymphatics from previous radiation or surgery, malignant obstruction, or recurrent episodes of cellulitis). Primary lymphedema begins before the age of 40 years, may be bilateral (50% of cases), and affects women 10 times more often than men. 178 LYMPHEDEMA Secondary lymphedema from infection, radiation, or surgery affects men and women of all ages, is usually unilateral, and is preceded by the characteristic history. Malignant obstruction affects patients older than 40 years and is almost always unilateral (>95% of cases). The most common cause of malignant lymphedema in the leg is metastatic prostate carcinoma in men and lymphoma in women. Lymphedema of the arm is almost always due to breast cancer, either the tumor itself or combined treatment with surgery and radiation. 179  Acute edema (onset < 72 hrs) Unilateral Unilateral or bilateral? Bilateral Or significant asymmetry Evaluate for DVT Consider medication side effect or high sodium load Bilateral DVT or IVC clot still Wells score for DVT possible Low High probability probability D-dimer Duplex US Normal Positive Negative DVT ruled out DVT ruled in Consider repeat ultrasound in Consider other diagnoses 1 week, specially if clinical suspicion is high 180 Wells criteria for DVT 181  Subacute or chronic edema (onset > 72hrs.) Pitting or non-pitting? Non-pitting Pitting Specific diagnosis suggested by history, Probable lymphedema focused exam, and basic labs? Also consider hypothyroidism (e.g.heart failure, renal failure, cirrhosis, chronic venous stasis) No Yes Work up relevant diagnosis Hypoalbuminemia withoust significant proteinuria, normal JVP → consider workig up liver disease with a RUQ ultrasound, also consider malnutrition. Hypoalbuminemia with significant proteinuria on UA, normal JVP→Quantify proteinurial and work-up possible nephrotic syndrome Normal albumin, elevated JVP→Check an ECHO to evaluate for HF & pulmonary hypertension 182 Management Mild oedema usually responds to elevation of the legs, compression stockings, or a thiazide or a low dose of a loop diuretic, such as furosemide or bumetanide. In nephrotic syndrome, renal failure and severe cardiac failure, very large doses of diuretics, sometimes in combination, may be required to achieve a negative sodium and fluid balance. Restriction of sodium intake and fluid intake may be required. Your Date Here Your Footer Here 183  Diuretics are not helpful in the treatment of oedema caused by venous or lymphatic obstruction or by increased capillary permeability. Clinical pearl! Your Date Here Your Footer Here 184  Proteinuria Your Date Here Your Footer Here Proteinuria While very small amounts of high-molecular-weight proteins and moderate amounts of low-molecular-weight proteins pass through the healthy GBM, these proteins normally are completely reabsorbed by receptors on tubular cells. Hence, in healthy individuals, less than 150 mg of protein is excreted in the urine each day, much of which is derived from tubular cells. This includes Tamm–Horsfall protein (uromodulin), encoded by the UMOD gene that has recently been linked to tubulo-interstitial disease. Your Date Here Your Footer Here 186  The presence of larger amounts of protein is usually indicative of significant renal disease. Clinical pearl! Your Date Here Your Footer Here 187 Proteinuria Proteinuria is usually asymptomatic and is often picked up by urinalysis, although large amounts of protein may make the urine frothy. Transient proteinuria can occur after vigorous exercise, during fever, in heart failure and in people with urinary tract infection. Patients should be assessed for the presence of these conditions and urine testing repeated once the potential trigger has been treated or resolved Your Date Here Your Footer Here 188 Orthostatic proteinuria Typically less than 1 g/24 hrs of protein is excreted only in association with an upright posture. The first morning sample being negative Benign disorder Does not require treatment. Your Date Here Your Footer Here 189  Testing for proteinuria is best done on an early morning sample That’s why! Your Date Here Your Footer Here 190 Microalbuminuria In healthy individuals, there is virtually no urinary excretion of large-molecular-weight serum proteins, such as albumin, in contrast to modest urinary excretion of tubule-derived proteins. The presence of even moderate amounts of albuminuria (previously referred to as microalbuminuria) is therefore abnormal, and may indicate early glomerular pathology, at a time when the standard dipstick test remains negative. Your Date Here Your Footer Here 191  Microalbuminuria is defined as Urine albumin excretion of 30–300 mg/day. Clinical pearl! Your Date Here Your Footer Here 192 Microalbuminuria in diabetics Screening for moderately elevated albuminuria should be performed regularly in patients with diabetes, as persistently elevated levels warrant therapy with inhibitors of the renin–angiotensin–aldosterone system, even in normotensive individuals, to reduce the rate of loss of renal function. Persistent moderately increased albuminuria has also been associated with cardiovascular mortality in patients with and without diabetes, but an explanation for this association has not yet been established. Your Date Here Your Footer Here 193 Overt (dipstick-positive) proteinuria Urinary dipstick testing is a valuable screening tool for the detection of proteinuria; it is only semi- quantitative, however, as it is highly dependent on the concentration of the urine. Typically, standard dipsticks test positive for protein once the urinary protein exceeds approximately 0.5 g/24 hrs; however, trace to 1+ on dipstick may be observed in very concentrated urine from individuals with no evidence of renal pathology. Your Date Here Your Footer Here 194 Protein Semi quantitative measurement of urine albumin, which is expressed on a scale from 0 to +++ or ++++. Number of (+) in dipstick Approximate amount of protein + 800 mg/l ++ 1450 mg/l +++ 3000 mg/l Your Date Here Your Footer Here 195  All patients with persistent proteinuria on dipstick should have the amount of protein quantified to guide further investigations Clinical pearl! Your Date Here Your Footer Here 196 Quantification Since quantification by 24-hour urine collection is often inaccurate, the protein:creatinine ratio (PCR) in a spot sample of urine is preferred. This makes an allowance for the variable degree of urinary dilution and can be used to extrapolate to 24- hour values. Changes in PCR also give valuable information about the progression of renal disease and response to therapy in CKD. Your Date Here Your Footer Here 197 Quantification Your Date Here Your Footer Here 198  When more than 1 g of protein per day is being excreted, glomerular disease is likely and this is an indication for renal biopsy Clinical pearl! Your Date Here Your Footer Here 199 Quantification It is possible to measure albumin:creatinine ratio (ACR), but this requires a more expensive immunoassay and is usually reserved for situations when high sensitivity is required, such as detection of the early stages of diabetic nephropathy. Your Date Here Your Footer Here 200 Identifying the type of protein in urine Large amounts of low-molecular-weight proteins, such as β2-microglobulin (molecular weight 12 kDa), in the urine suggest renal tubular damage and are referred to as tubular proteinuria. This rarely exceeds 1.5–2 g/24 hrs. tubulointerstitial nephritis, analgesics nephropathy are examples of tubular proteinuria. Your Date Here Your Footer Here 201 Identifying the type of protein in urine Free immunoglobulin light chains (molecular weight 25 kDa) are filtered freely at the glomerulus but are poorly identified by dipstick tests. Hence, electrophoresis of the urine and specific immunodetection methods are required to detect immunoglobulin light chains, known as ‘Bence Jones protein’. This may occur in AL amyloidosis and in B-cell dyscrasias but is particularly important as a marker for myeloma Your Date Here Your Footer Here 202 Investigation of proteinuria Your Date Here Your Footer Here 203  Oliguria Your Date Here Your Footer Here Definition Oliguria is defined as being present when less than 400 mL of urine is passed per day Anuria is deemed to exist when less than 100 mL of urine is passed per day. Your Date Here Your Footer Here 205 Oliguria The volume of urine produced represents a balance between the amount of fluid that is filtered at the glomerulus and that reabsorbed by the renal tubules. When GFR is low, urine volumes may still be normal if tubular reabsorption is also reduced; hence urine volume alone is a poor indicator of the severity of kidney disease. Your Date Here Your Footer Here 206 Oliguria Oliguria and anuria may be caused by a reduction in urine production, as in pre-renal AKI, when GFR is reduced and tubular homeostatic mechanisms increase reabsorption to conserve salt and water. A high solute load or associated tubular dysfunction may, however, produce normal or high urine volumes in such cases until the pre-renal insult becomes severe and GFR is markedly reduced, such as occurs in diabetic ketoacidosis with marked glycosuria. Urine volumes are variable in AKI due to intrinsic renal disease, but a rapid decline in urine volume may be observed. Your Date Here Your Footer Here 207 Oliguria Obstruction of the renal tract can produce oliguria and anuria, but to do so, obstruction must be complete and occur distal to the bladder neck, be bilateral, or be unilateral on the side of a single functioning kidney. Unilateral ureteric obstruction may not lead to any noticeable reduction in urine output. Your Date Here Your Footer Here 208  The presence of pain that is exacerbated by a fluid load suggests an acute obstruction of the renal tract, and its characteristics may be of value in reaching a diagnosis. Clinical pearl! Your Date Here Your Footer Here 209 Oliguria Obstruction at the bladder neck is associated with lower midline abdominal discomfort. Ureteric obstruction typically presents as loin pain radiating to the groin. At the level of the renal pelvis may present as flank pain. Chronic obstruction rarely produces pain but may give rise to a dull ache. Urethral strictures should be considered as a possible cause, especially in patients with a history of instrumentation of the renal tract. Your Date Here Your Footer Here 210 Oliguria The presence of bladder enlargement in a middle-aged or elderly man suggests benign or malignant enlargement of the prostate gland as a potential cause of oliguria or anuria. It is important to note that many cases of acute urinary retention are observed after general anaesthesia, particularly in patients with pre-existing prostatic enlargement. Partial obstruction can be associated with a normal or even high urine volume due to chronic tubular injury, which causes loss of tubular concentrating ability. Your Date Here Your Footer Here 211  Management of oliguria and anuria should be directed at the underlying cause Clinical pearl! Your Date Here Your Footer Here 212 Causes of anuria Your Date Here Your Footer Here 213  Polyuria Your Date Here Your Footer Here Definition Polyuria is defined as a urine volume in excess of 3 L/24 hrs. Your Date Here Your Footer Here 215 Causes Your Date Here Your Footer Here 216 Investigations measurement of urea, creatinine and electrolytes, glucose, calcium and albumin. A 24-hour urine collection may be helpful to confirm the severity of polyuria. The presence of nocturnal polyuria suggests a pathological cause. Your Date Here Your Footer Here 217 THANK YOU! Do you have any questions?