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Michael Song michael.song21@imperial.ac.uk Renal/Urology - Chronic renal and UTIs MedEd Y3 Written Exam Lectures 2023 Slides adapted from Sharan KapadiaSESSION STRUCTURE Aetiology History Presentation Investigations Management = Gold Standard = High YieldSESSION CONTENT • Chronic Kidney Disease (CKD) • Polycystic Kidney Disease (PKD) • Renal Artery Stenosis (RAS) • Amyloidosis • Renal Cell Carcinoma (RCC) • UTIs Case 1 A 65 M has aswollen face and ankles for the past 2 weeks. The patient has a15-year history of type 2 diabetes mellitus. He reports feeling exhausted and ‘run-down’ recently. Temperature is 37.3 C, BP 153/99 mm Hg, HR is 70/min. Physical examination shows periorbital edema, bilateral pitting edema in the lower extremities, and reduced light touch sensation in the feet. Which of the following laboratory values is most likely to be elevated in this patient? a) Albumin b) Calcium c) Creatinine d) Sodium e) Urea Case 1 A 65 M has a swollen face and ankles for the past 2 weeks.The patient has a 15-year history of type 2 diabetes mellitus. He reports feeling exhausted and ‘run-down’ recently. recently. Temperature is 37.3 C, BP 153/99 mm Hg, HR is 70/min. Physical examination shows periorbital edema, bilateral pitting edema in the lower extremities, and reduced light touch sensation in the feet. Which of the following laboratory values is most likely to be elevated in this patient? a) Albumin b) Calcium c) Creatinine d) Sodium e) UreaCKD – Aetiology & Kidney functions Chronic damage to glomeruli-> remodelling abnormal kidney structure -> gradual lossof kidney function A WET BED Function Pathological effect Acid-base balance Metabolic acidosis Water removal peripheral/pulmonary oedema Erythropoietin production Normocytic normochromic anaemia Toxin removal Uraemia, hyperphosphataemia Blood pressure control HTN, CVD Electrolyte balance Hyperkalaemia D - Vitamin D activation HypocalcaemiaCKD – Epidemiology • Common Condition • age-standardized global prevalence of ~9% for CKD stages 3–5 • More common in women • ~10% in women • ~5% in men • Risk increases exponentially with age • 0.5%: 18–39 years • 6.7%: 40–59 years • 92.9%: 60 years or over • Black and Hispanic populations at higher risk • FHx of renal disease increases riskCKD – Risk Factors Think what would strain the glomerular apparatus and cause chronic renal damage ➢ Diabetes mellitus – most common cause (~30-50%) ➢ Hypertension – 2 most common cause ➢ Medications (eg.heavy NSAIDuse) ➢ 1º glomerular diseases (eg. glomerulonephritis) ➢ Systemic disease (eg.SLE) ➢ Obstructive uropathiesCKD – Presentation Early signs and symptoms • Generally unwell (fatigue) • Flank masses • Polyuria, nocturia (ADPKD) • Hypertension • Bladder distension • Oedema (obstructive) Later signs and symptoms • Reduced urine output (oliguria/anoria) • SOB (fluid overload) • Uraemia symptoms (N+V, pruritus, appetite loss, cramps) • Pallor (anaemia) • Frothy urine (proteinuria) • Systemic symptoms (CV, neuro, MSK, acidosis) Symptoms of CKD often go unnoticed until the disease has significantly progressed because the kidneys can compensate for their diminished function in the early stagesCKD – Investigations • First test = urine dipstick Creatinine levels do • Look for haematuria (to rule out glomerulonephritis etc) depend on muscle • Exclude UTI mass etc. So, the eGFR ➢ Urine dipstick is NOT good at assessingproteinuria to diagnose CKD; based on creatinine is the 3 tests below should be used instead only an estimate. 1. Albumin creatinine ratio (ACR) – early morningmid stream urine sample 2. Serum creatinine 3. eGFR ➢ Cannot eat meat for at least 12hours before test ➢ Repeat in 6 months then 3months – to see chronic picture • BMI, BP,HbA1c, lipid profile – assess CV risk factors • CV events = most common cause of death in CKDpatients • Renal USS if indicated – suspect urinary tract stones or ADPKDCKD – Stages 3, 30 Stages 1-5 = * * *no CKD if eGFR ≥60 and no signs of kidney damage, e.g. abnormal U&Es, proteinuria 15, 30, 45, 60, 90 Source: https://geekymedics.com/chronic-kidney-disease/CKD – Management Significant HTN / proteinuria Lifestyle • ACEi / ARB • Exercise • SGLT2 • Maintain healthy weight Significant anaemia • Good glycaemic control • Iron studies + oral iron (first) • Good BP control • EPO • Smoking cessation Renal replacement therapy Reduce CV risk factors! • Peritoneal dialysis • Renal transplantADPKD • Definition: Autosomal dominant condition; multiple cysts in kidneys; destroy parenchyma • Aetiology &RFs: proliferative pathology whereby the epithelium makes cysts • 2 types: [ADPKD1] (chromosome 16) and [ADPKD2] (chromosome 4) • [ADPKD1] more common, more severe and earlier onset • Epidemiology: Middle age, most common inherited kidney disorder,most common heritable cause of CKD • Presentation: Large bilateral flank masses, flank pain, haematuria, HTN, recurrent UTI • Associations: CKD,liver cysts (most common extrarenal manifestation~70%), Berry aneurysms (SAH), CVD (e.g. mitral valve prolapse),cystsin other organs • Diagnosis: USS - shows multiple cysts in kidneys • Management: No cure, focus on symptom control / complication management Tolvaptan (vasopressin receptor 2 antagonist) – only for some patientsRenal Artery Stenosis (RAS) • Definition: Stenosis and narrowing of the renal artery • Aetiology & RFs: 2 types: • atherosclerotic (90%) – build up of plaque • fibromuscular dysplasia (10%) – abnormal development of cells in walls of renal artery • Epidemiology: • Atherosclerotic → men with atherosclerotic CV risk factors • Fibromuscular dysplasia → young women • Presentation: Sudden-onset, resistant hypertension (RAAS activation) • ischaemic nephropathy, flash pulmonary oedema (ie. due to dramatic acute decompensated heart failure), aneurysms, CKD • Diagnosis: First-line = duplex USS; most ‘useful’ = CTA; gold standard is DSA • Management: CV risk control, BP control, revascularisation, stentingAmyloidosis • Definition: Multisystem disease due to deposition of abnormal fibrillar protein (amyloid) • Types: • Type I [AL amyloidosis] = amyloidosis light chain – most common type • Type II is [AA amyloidosis] = serum amyloid A protein • Familial is [ATTR amyloidosis] = transthyretin amyloidosis • Presentation: Nonspecific – dyspnoea, weight loss, fatigue • Multisystem – Renal, Cardiac, GI, Neuro, MSK • “A lady with a 20-year history of rheumatoid arthritis has nephrotic syndrome” Chronic inflammatory disease + nephrotic syndrome = SAA • Diagnosis: • Congo red staining: apple-green birefringence • Serum amyloid precursor (SAP) scan. • Gold standard is biopsy of skin, rectal mucosa or abdominal fat; fat pad is most easily accessibleAmyloidosis Congo red staining – used to detect amyloid structure of Apple green birefringence under polarised light – if protein aggregates amyloidosis is present, when sample is stained with Congo red and held under polarised light, there will be apple-green birefringenceRenal Cell Carcinoma (RCC) • Definition: Malignancy of kidney; most common type is clear cell adenocarcinoma; originates from proximal convoluted tubule (PCT) cells • Epidemiology: Most common 1º renal malignancy; middle aged men (50-70 year olds) • Aetiology: Gene deletion on chromosome 3 (acquired / inherited as part of von Hippel- Lindau (vHL) syndrome) • RFs: von Hippel-Lindau (vHL) syndrome, smoking, tuberous sclerosis • Investigations: • Bloods: LFT, LDH, FBC, U&E, Ca (rule out differentials) • Scans • USS – initial (distinguish from benign lesions) • CT abdomen and pelvis with IV contrast (± US abdomen, blood and urine testing)https://www.mdpi.com/2076-3417/11/13/6076RCC - Presentation Classic triad (uncommon ~10%, suggests locally advanced disease) ~ 50% RCCs are • flank pain, hematuria, palpable mass detected incidentally on ultrasound and CT ± FLAWS imaging Paraneoplastic syndromes • PTH - hypercalcaemia • EPO - polycythaemia • ACTH - cushing’s • Renin - HTN • Stauffer syndrome (ALT/AST) – hepatic dysfunction Other: • Varicocoele (renal vein compression, majority left-sided) “Bagof worms” • Lower limb oedema (IVC compression)RCC - Diagnosis T (primary tumour) N (lymph nodes) M (metastases) TX: primary tumour cannot be assessed NX: regional lymph nodes cannot be assessed T0: no evidence of primary tumour N0: no regional lymph M0: no distant node metastasis metastasis T1: tumour confined to the kidney,and ≤7 cm in greatest N1: metastasis in regional M1: distant dimension lymph node(s) metastasis. T2: tumour confined to the kidney,and >7 cm in greatest dimension T3: tumour extends into major veins or perinephric tissue, but not into the ipsilateral adrenal gland and not beyond Gerota fascia T4: tumour invades beyond Gerota fascia (including contiguous extension into the ipsilateral adrenal gland).RCC - Treatment Classification Early-stage Partial nephrectomy if organ-confined T1 T2 Radical nephrectomy Locally advanced Radical nephrectomy + lymph node dissection T3 / T4 Neo-Adjuvant Therapy: Tyrosine kinase inhibitors (TKIs) or immunotherapy can be considered to downsize the tumour before surgery. Metastatic Cytoreductive nephrectomy - patientswith good performance status M1 Low risk patients: VEGF inhibitors such as sunitinib,bevacizumab or pazopanib. Intermediate and high risk patients: dual immunotherapy with ipilimumab and nivolumab Case 2 A 32 F comes to see her GP due to aburning sensation when urinating.She has been urinating 4-5 times aday, which is more frequent than usual.She reports no subjective fevers, abdominal pain, or blood in her urine. Vital signs are normal. Urine dipstick reveals: RBC: Negative WBC: 2+ Leukocyte esterase: + Nitrites: + What is the next best step in management? a) Recommend good hydration only b) Recommend good hydration and cranberry juice only c) Prescribe oral nitrofurantoin d) Perform renal ultrasound e) Send urine sample for culture Case 2 A 32 F comes to see her GP due to aburning sensation when urinating.She has been urinating 4-5 times aday, which is more frequent than usual.She reports no subjective fevers, abdominal pain, or blood in her urine. Vital signs are normal. Urine dipstick reveals: RBC: Negative WBC: 2+ Leukocyte esterase: + Nitrites: + What is the next best step in management? a) Recommend good hydration only b) Recommend good hydration and cranberry juice only c) Prescribe oral nitrofurantoin d) Perform renal ultrasound e) Send urine sample for cultureUTIs – definition(s) • UTIs = infection of upper or lower urinary tract; defined on culture as >100,000CFUs (colony formingunits) • Lower UTIs = infection of bladder (also known as cystitis) • Upper UTIs = infection has ascended to ureters and kidneys (also known as pyelonephritis - EMERGENCY) • Recurrent UTIs = ≥2in 6 months and ≥3in a year • Catheter associated UTI = upper or lower UTI in someone with a catheter ≥48hours • Asymptomatic bacteriuria = bacteria in the urine but no signs or symptomsUTIs – Aetiology • Can occur when bacteria from GI tract enter GU tract via: • Ascension • Haematogenous spread • Direct inoculation E. coli Most common cause in UK overall S. saprophyticus Common cause in young, sexually active women P. mirabilis Common cause in people with chronic UTI and staghorn kidney stones KlebsiellaUTIs – RFs, Epidemiology, Prognosis • UTIs happen in 50% of women; 1/3 of women by 24 • Resolves in 3-5 days • 20-30% recurrence rates • In young and pre-menopausal women : • PMHx of UTIin childhood • Recurrent sexual intercourse and contraceptive diaphragm • Pregnancy • In post-menopausal and elderly women : • Hx of UTI before menopause • Urinary incontinence, high post-void volume, cystocele, catheters, poor ADLs • Atrophic vaginitis (thinning of vagina walls due to low oestrogen) • Urethral instrumentation and catheterisationUTIs – Presentation • Features ➢ Change in urine: cloudy / bloody / offensive smelling ➢ Urinary symptoms such as dysuria, polyuria, urgency ➢ Suprapubic discomfort / tenderness ➢ Delirium, confusion, acting strange in atypical cases (elderly) • Lower vs upper UTI (presence = red flag for upper UTI) ➢ Low grade/no fever with lower UTIs ➢ No costovertebral angle (CVA) tenderness with lower UTIs ➢ No vital sign derangements in lower UTIUTIs – Investigations • First-line = urine dipstick – to check for nitrites, LE, WBCs, RBCs ➢ Unreliable in women >65 and if catheterised – asymptomatic bacteriuria Nitrite Leukocyte / RBC Consideration WBC + + + Likely UTI - + + Send for culture to confirm - - - Consider other diagnoses • Send a MSU to the lab for culture if complicated: • Pregnant, plastic, paediatric, persistent, peeing bloodUTIs – Management • Simple analgesia • Assess for sepsis risk or risk of upper UTI - changes management Patient Treatment Men Nitrofurantoin or Trimethoprim for 7 days Non-pregnant women Nitrofurantoin or Trimethoprim for 3 days Pregnant women 1. Nitrofurantoin for 7days (contraindicated near term) 2. Amoxicillin or Cefalexin for 7days Avoid Trimethoprim Catheterised / elderly patients Asymptomatic: don’t treat Symptomatic: 7days Abxas above Acutepyelonepthritis IV fluids, analgesia, anti-emetics Cefalexin or Quinolone (for non-pregnant women) for 10-14daysUTIs – Complications ➢ Pyelonephritis ➢ Sepsis ➢ Renal abscess ➢ Renal papillary necrosis SBA 1 A 64 F comes to the GP due to dysuriaand urinary urgency. She reports feeling unwell for the past several days. On examination, the patient’s lips appear dry, and her eyes are sunken. She squirms when pressure is applied at the paravertebral region. The patient mentions she has not eaten in 2 days. Urine dipstick findings are consistent with a urinary tract infection. What is the next best step in management for this patient? a) Send urine for culture b) Start intravenous ceftriaxone c) Start intravenous dextrose d) Start intravenous 0.9% NaCl e) Start intravenous 3% NaCl SBA 1 A 64 F comes to the GP due to dysuriaand urinary urgency. She reports feeling unwell for the past several days. On examination, the patient’s lips appeardry, and her eyes are sunken. She squirms when pressure is applied at the paravertebral region. The patient mentions she has not eaten in 2 days. Urine dipstick findings are consistent with a urinary tract infection. What is the next best step in management for this patient? a) Send urine for culture b) Start intravenous ceftriaxone c) Start intravenous dextrose d) Start intravenous 0.9% NaCl e) Start intravenous 3% NaCl SBA 2 (hard) A 54 F comes to her GP due to “swelling around the feet and eyes” forthe past several weeks. She has been feeling tired and ”lacks motivation” to do anything. Medical history is significant for chronic vertebral osteomyelitis of several years’ duration that is being managed under specialist care, and a diagnosis of type 2 diabetes mellitus 6 months ago. She takes ibuprofen occasionally to manage the pain from her osteomyelitis. Urine dipstick reveals proteinuria. What is the most likely mechanism behind this patient’s condition? a) Chronic renal hypoperfusion and free radical damage b) Compressive destruction of nephrons by fluid-filled epithelial structures c) Deposition of acute phase reactant proteins d) Deposition of immunoglobin light chains e) Glycation of glomerular vessels SBA 2 (hard) A 54 F comes to her GP due to “swelling around the feet and eyes” forthe past several weeks. She has been feeling tired and ”lacks motivation” to do anything. Medical history is significant for chronic vertebral osteomyelitis of several years’ duration that is being managed under specialist care, and a diagnosis of type 2 diabetes mellitus 6 months ago. She takes ibuprofen occasionally to manage the pain from her osteomyelitis. Urine dipstick reveals proteinuria. What is the most likely mechanism behind this patient’s condition? a) Chronic renal hypoperfusion and free radical damage b) Compressive destruction of nephrons by fluid-filled epithelial structures c) Deposition of acute phase reactant proteins d) Deposition of immunoglobin light chains e) Glycation of glomerular vessels CKD GFR range Chronic Kidney Disease: summary slide stage 1 >90 ml/min Aetiology: Examination: Investigations: 2 60-90ml/min 3a 45-59ml/min Abnormalityof kidney 3b 30-44ml/min structure/function present Pallor Urine dipstick: Diagnosis determined by: • ↑serum Cr • proteinuria or haematuria, 4 15-29ml/min for OVER3 MONTHS • Haematuria and/or • reduction in eGFR>3 months 5 <15 ml/min Most common = Diabetes and Differentials: Hypertension proteinuria AKIvs. CKD: • Electrolyte • Renal ultrasound → CKD= bilateralsmallkidneys Other: UTI abnormalities • Heavyanalgesic use • Exceptions: ADPKD, diabetic nephropathy (early • Chronicglomerulonephritis eGFR <60 or <90 + stages), amyloidosis or pyelonephritis or ADPKD Malignancy • CKD= hypocalcaemia symptoms History: Management: Complications: Swollen – oedema ✶ Cardiovascular death Lifestyle changes Polyurea st ✶ Anaemia (reduce EPO) 1 line medical: controlhypertension (ACEi) + diabetes (SGLT2i) FLAWS +insomnia +N&V optimally Bonedisease: Pruitus (uraemia) nd ✶ LowVit. D, High PO4, low Ca 2 line medical: non-dihydropyridine CCBs – diltiazem + verapamil ✶ Secondaryhyperparathyroidism ✶ Management: dietary, vit. D If ADPKD: flankmasses If amyloid: clues in history tablets, phophate bindersUrinary TractInfection: Summary slide Aetiology: Investigations: Examination: • Translocation of GI bacteria to GU tract • First-line: URINE DIPSTICK ➔ positiveleucocyte Suprapubic tenderness;CVA tenderness 5 if pyelonephritis • Presence of a pure growth of > 10 esteraseand nitrites colony forming units per mL of fresh MSU • E.coli= most common • Gold-5tandard: UrineMC&S ➔ URINE MSU: Differentials: >10 CFU/mL; pyelonephritis ➔ whitecell casts Risk Factors: • Sexual activity Pyelonephritis • Woman > Men • Postmenopausal • Imaging: Abdominal Ultrasound to rule out • Age>50 • Catheterisation urinary tract obstruction GU syndromeof menopause Signs/Symptoms: STI Management: Urolithiasis Lower UTI: Lower UT symptoms (Prostatitis + Cystitis): • Urinary Frequency, Urgency, Dysuria + • Non-Pregnant Woman: Complications: Haematuria, Foul-smelling±cloudy Trimethoprim/Nitrofurantoin for 3 days • Pregnant Woman: urine, Suprapubic/loin pain and low- ✶ Pyelonephritis grade fever. Nitrofurantoin/Amoxicillin for 7 days • Men: Trimethoprim/Nitrofurantoin for 7 Upper UT symptoms (Pyelonephritis): days ✶ Renal abscess • Fevers + Rigors+ Flank Pain Pyelonephritis: Cefalexin for10-14 days ✶ Septic shock Michael Song michael.song21@imperial.ac.uk Thanks for listening :) Any questions? Slides Adapted from Sharan KapadiaPlease fill out if you have any feedbackl! SBA 1 A 63 M presentswith frank haematuria. but report no changes to passing urine. They report feeling quite tired the last few months and theirclothes have felt looser. They are an ex-smoker with a 46 pack-year history. Examination: HR 72 bpm, BP 165/80 mmHg, O2 sats 96% on airand temp 37.2ºC. On palpation he has tenderness in the and non-tender.e and a ballotable mass on the left side of the abdomen. On digital rectal exam his prostate is not enlarged What is the most likely diagnosis? a) Urolithiasis b) STI c) Renal cell carcinoma d) LowerUTI e) Pyelonephritis SBA 2 A 69 M arrives at their GP due to painless blood in their urine. They recently began complaining of a mild testicularache. He is a heavy smoker smoking 60 cigarettes a day for47 years. On examination he iscachectic and hasa palpable mass on the left side of the abdomen. His bloods reveals anaemia. Urine dip results: What would you most likely find in a testicular examination? Leukocytes ++ a) Normal Blood +++ b) “Bag of worms” Protein + c) Hard painful testicle Nitrites Negative d) Swelling eased by elevating testes Glucose Trace e) Soft, fluctuant lump SBA 3 A 75-year-old man with stage 4 chronic kidney disease presents with increased SOB and tiredness. Hisrecent blood tests are shown: Hb Woman: (115-160) MCV (82 - 100) Platelets (150 - 400) WBC (4.0 - 11.0) Na+ (135 - 145) What is the next most appropriate step in management? K+ (3.5 - 5.0) Bicarbonate (22 -29) a) Send blood for iron studies b) Prescribe oral EPO Urea (2.0 -7.0) c) Prescribe IV EPO Creatinine (55-120) d) Prescribe IV iron supplementation e) Send blood for EPO level SBA 4 A 44 M has been visiting his general practice (GP) frequently due to persistently high blood pressure at 155/95 mmHg resistant to anti-hypertensive medications. He has a PMHx of recurrent UTI and FHx of renal conditions diagnosed at a youngage. His father and grandfatherhave had heart problems and died from a stroke. His GP thus arranged for an ultrasound scan ofthe abdomen and urinary tract which revealed multiple cysts on both kidneys. What is the most common extrarenal manifestation of this condition? a) Stroke b) Aortic dissection c) Berry aneurysms d) Mitral valve prolapse e) Liver cysts SBA 5 A 25 F visits her GP due to blood in her urine. She describes a discomfort and a burning sensation during urination and 39 weeks pregnant.described to have a foul smell. She has not other significant symptoms other than a mild fever. She is What is the most appropriate treatment? a) Nitrofurantoin 7 days b) Nitrofurantoin 3 days c) Amoxicillin 7 days d) Trimethoprim 3 days e) Trimethoprim 7 days