Nephrology Passmedicine 2024 PDF

4/6/24, 2:57 PM PassMedicine PassMedicine Question 1 of 244 X p Which one of the following is least recognised as a cause of membranous glomerulonephritis? Malaria...

4/6/24, 2:57 PM PassMedicine PassMedicine Question 1 of 244 X p Which one of the following is least recognised as a cause of membranous glomerulonephritis? Malaria 23% Lymphoma 9% Hepatitis B 11% Cryoglobulinaemia 42% Gold 15% 6 9 0 Discuss (5) Improve Next question Membranous glomerulonephritis Membranous glomerulonephritis is the commonest type of glomerulonephritis in adults and is the third most common cause of end-stage renal failure (ESRF). It usually presents with nephrotic syndrome or proteinuria. Renal biopsy demonstrates: electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. This creates a 'spike and dome' appearance Causes idiopathic: due to anti-phospholipase A2 antibodies infections: hepatitis B, malaria, syphilis malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia drugs: gold, penicillamine, NSAIDs autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid https://www.passmedicine.com/v7/question/questions.php?q=0 1/3 4/6/24, 2:57 PM PassMedicine Management all patients should receive an ACE inhibitor or an angiotensin II receptor blocker (ARB): these have been shown to reduce proteinuria and improve prognosis immunosuppression as many patients spontaneously improve only patient with severe or progressive disease require immunosuppression corticosteroids alone have not been shown to be effective. A combination of corticosteroid + another agent such as cyclophosphamide is often used consider anticoagulation for high-risk patients Prognosis - rule of thirds one-third: spontaneous remission one-third: remain proteinuric one-third: develop ESRF Good prognostic features include female sex, young age at presentation and asymptomatic proteinuria of a modest degree at the time of presentation. Next question                Textbooks High-yield textbook https://www.passmedicine.com/v7/question/questions.php?q=0 2/3 4/6/24, 2:57 PM PassMedicine Extended textbook Links American Society of Nephrology 8 4 2017 Primary Membranous Nephropathy review Royal College of Physicians 4 5 2012 Membranous nephropathy review Report broken link Media Membranous glomerulonephritis (membranous nephropathy) Osmosis - YouTube 39 7 Report broken media Score: 0% 1 All contents of this site are © 2024 Passmedicine Limited Back to top https://www.passmedicine.com/v7/question/questions.php?q=0 3/3 4/6/24, 2:58 PM PassMedicine PassMedicine Question 2 of 244 A 34-year-old woman presents to your GP clinic for ongoing investigation of her hypertension. She has recently completed ambulatory blood pressure monitoring which found an average blood pressure of 152/98mmHg. Examination is unremarkable. βHCG is negative. She is normally fit and well apart from a history of childhood asthma. She is teetotal but smokes 5 cigarettes a day. Her father passed away last year at the age of 62 from a stroke. Urine dip is normal. You suspect fibromuscular dysplasia. Which of the following investigation results would be most typical in fibromuscular dysplasia? Echocardiogram showing left outflow obstruction 9% Serum cholesterol >7 4% Ultrasound renal tracts showing asymmetric kidneys 74% MRI abdomen showing solitary adrenal mass 5% Electrolyte profile showing hypokalaemia 8% Young female, hypertension and asymmetric kidneys → fibromuscular dysplasia Important for me Less important A patients who is young, female, hypertension and has asymmetric kidneys with a normal urine dip should prompt consideration of fibromuscular dysplasia. Assymmetric kidneys are often first noted on ultrasound; imaging of the vessel is done by duplex and most accurately by contrast catheter angiography of the renal artery. Examination was unremarkable and there are no symptoms of cardiovascular disease. Left outflow obstruction would be found in coarctation of aorta, another secondary cause of hypertension. Fibromuscular dysplasia is not an atherosclerotic process and it does not have the same modifiable 'lifestyle' risk factors as renal artery stenosis, including hypercholesterolaemia. https://www.passmedicine.com/v7/question/questions.php?q=0 1/3 4/6/24, 2:58 PM PassMedicine Conn's syndrome and phaeochromocytoma might present with an adrenal mass. Conn's syndrome might also present with hypokalaemia. 6 9 0 Discuss (7) Improve Next question Fibromuscular dysplasia Renal artery stenosis secondary to atherosclerosis accounts for around 90% of renal vascular disease, with fibromuscular dysplasia being the most common cause of the remaining 10%. Epidemiology 90% of patients are female Features hypertension chronic kidney disease or more acute renal failure e.g. secondary to ACE-inhibitor initiation 'flash' pulmonary oedema Next question                Textbooks High-yield textbook Extended textbook https://www.passmedicine.com/v7/question/questions.php?q=0 2/3 4/6/24, 2:59 PM PassMedicine PassMedicine Question 3 of 244 A 33-year-old man who undergoes peritoneal dialysis attends the emergency department with a 2-day history of abdominal pain, nausea, vomiting and fevers. He also noted his dialysis solution was more cloudy when it was last changed. On examination, his abdomen is generally tender and he is febrile at 39.3ºC. His blood tests are shown below: Male: (135-180) Hb 136 g/L Female: (115 - 160) Platelets 389 * 109/L (150 - 400) WBC 13.9 * 109/L (4.0 - 11.0) CRP 221 mg/L (< 5) A chest x-ray is performed which shows no focal consolidation, and a urine dip is clear. What is the most likely causative organism of his symptoms? Escherichia coli 14% Mycoplasma pneumoniae 1% Pseudomonas aeruginosa 3% Staphylococcus epidermidis 79% Streptococcus pyogenes 3% Coagulase-negative Staphylococcus is the most common cause of peritonitis secondary to peritoneal dialysis Important for me Less important Staphylococcus epidermidis is correct, this is a coagulase-negative Staphylococcus found on the skin. It is a common cause of peritonitis in those undergoing peritoneal dialysis. https://www.passmedicine.com/v7/question/questions.php?q=0 1/3 4/6/24, 2:59 PM PassMedicine Escherichia coli is incorrect. Escherichia coli is the most common cause of urinary tract infections and spontaneous bacterial peritonitis in those with ascites. Mycoplasma pneumoniae is incorrect. This is a cause of atypical pneumonia, and classically causes bilateral consolidation on the chest x-ray. Pseudomonas aeruginosa is incorrect. Pseudomonas aeruginosa is a common cause of infective exacerbations in bronchiectasis and cystic fibrosis. Streptococcus pyogenes is incorrect. This is a beta-haemolytic group A streptococcus that can cause a variety of infections including cellulitis, necrotising fasciitis and scarlet fever. å 9 0Discuss (2) Improve Next question Peritoneal dialysis Peritoneal dialysis (PD) is a form of renal replacement therapy. It is sometimes used as a stop-gap to haemodialysis or for younger patients who do not want to have to visit hospital three times a week. The majority of patients do Continuous Ambulatory Peritoneal Dialysis (CAPD), which involves four 2-litre exchanges/day. Complications peritonitis o coagulase-negative staphylococci such as Staphylococcus epidermidis is the most common cause. Staphylococcus aureus is another common cause o antibiotics should cover both Gram positive and Gram negative organisms o the BNF recommends vancomycin (or teicoplanin) + ceftazidime added to dialysis fluid OR vancomycin added to dialysis fluid + ciprofloxacin by mouth o aminoglycosides are sometimes used to cover the Gram negative organisms instead of ceftazidime sclerosing peritonitis Next question                https://www.passmedicine.com/v7/question/questions.php?q=0 2/3 4/6/24, 2:59 PM PassMedicine Textbooks High-yield textbook Extended textbook Links Royal College of Physicians 7 7 £ 9 2012 End-stage renal disease review Report broken link Score: 0% 1 x 2 X 3 X All contents of this site are © 2024 Passmedicine Limited Back to top https://www.passmedicine.com/v7/question/questions.php?q=0 3/3 4/6/24, 2:59 PM PassMedicine PassMedicine Question 4 of 244 A 79-year-old man is admitted to the geriatric ward following a fall and is awaiting physiotherapy before discharge. While on the ward, he tells the team he suffers from recurrent bouts of abdominal pain. He describes them as shooting down to his groin on the right side. Physical examination is normal. A non-contrast CT is performed, showing multiple right-sided renal calculi. His relevant tests are shown below: Serum calcium 2.4 mmol/L (2.1-2.6) Urinary calcium:creatinine ratio 0.9 mmol/L (0.3-0.7) What is the most appropriate management to prevent further renal stone formation? Allopurinol 6% Bendroflumethiazide 71% Furosemide 7% Penicillamine 4% Sodium bicarbonate 12% In a patient with hypercalciuria and renal stones, calcium excretion and stone formation can be decreased by the use of thiazide diuretics Important for me Less important Bendroflumethiazide is correct. This patient has renal stones and hypercalciuria. The most likely type of renal stone in this patient is calcium oxalate. Adequate hydration and using thiazide diuretics to decrease the excretion of calcium into the urine can reduce the formation of these stones. Allopurinol is incorrect. This patient has renal stones on a background of hypercalciuria. The most common type of renal stone is calcium oxalate, which is even more likely in this patient, given his https://www.passmedicine.com/v7/question/questions.php?q=0 1/7 4/6/24, 2:59 PM PassMedicine hypercalciuria. Allopurinol is used in the prevention of urate renal stones, but there is no mention of gout or examination findings suggesting excess urate as a cause for his renal stones. This answer is, therefore, incorrect. Furosemide is incorrect. Loop diuretics indirectly increase calcium excretion into the urine, promoting calcium renal stones formation. Thiazide diuretics decrease urinary calcium excretion, so these would be used to prevent calcium oxalate stones. Penicillamine is incorrect. Penicillamine is used in patients with cystine stones to reduce stone formation by increasing the solubility of the cystine in urine. It is not used to prevent calcium oxalate stones. This patient has hypercalciuria and has developed renal stones, meaning the most likely constituent of his renal stones is calcium oxalate rather than cystine. Sodium bicarbonate is incorrect. This patient has renal stones on a background of hypercalciuria; he likely has calcium oxalate renal stones. Urate and cystine renal stones form more readily in acidic urine, and sodium bicarbonate may be used to alkalinise the urine and prevent these stones from forming. However, it is not used in the prophylaxis of calcium oxalate stones. Discuss Improve Next question Renal stones: management The British Association of Urological Surgeons (BAUS) published guidelines in 2018 and NICE in 2019 on the management of acute ureteric/renal colic. Initial management of renal colic Pain management and medical therapy both BAUS and NICE recommend an NSAID as the analgesia of choice for renal colic NICE whilst diclofenac has been traditionally used the increased risk of cardiovascular events with certain NSAIDs (e.g. diclofenac, ibuprofen) should be considered when prescribing if NSAIDs are contraindicated or not giving sufficient pain relief NICE recommend IV paracetamol the CKS guidelines suggest for patients who require admission: 'Administer a parenteral analgesic (such as intramuscular diclofenac) for rapid relief of severe pain' alpha blockers NICE promote smooth muscle relaxation and dilation of the ureter. potentially easing stone passage https://www.passmedicine.com/v7/question/questions.php?q=0 2/7 4/6/24, 2:59 PM PassMedicine NICE recommend these are considered for distal ureteric stones less than 10 mm in size BAUS don't formally recommend but do however acknowledge a recently published meta-analysis advocates the use of α-blockers for patients amenable to conservative management, with the greatest benefit amongst those with larger stones Initial investigations urine dipstick and culture serum creatinine and electrolytes: check renal function FBC / CRP: look for associated infection calcium/urate: look for underlying causes stone analysis should be considered once the stone has passed also: clotting if percutaneous intervention planned and blood cultures if pyrexial or other signs of sepsis Imaging non-contrast CT KUB should be performed on all patients, within 24 hours of admission NICE if a patient has a fever, a solitary kidney or when the diagnosis is uncertain an immediate CT KUB should be performed. In the case of an uncertain diagnosis, this is to exclude other diagnoses such as ruptured abdominal aortic aneurysm CT KUB has a sensitivity of 97% for ureteric stones and a specificity of 95% ultrasound should be used for pregnant women and children the sensitivity of ultrasound for stones is around 45% and specificity is around 90% Management of renal stones Simplified first-line NICE guidance (please see guidelines for more details) NICE Renal stones watchful waiting if < 5mm and asymptomatic 5-10mm shockwave lithotripsy 10-20 mm shockwave lithotripsy OR ureteroscopy > 20 mm percutaneous nephrolithotomy Uretic stones shockwave lithotripsy +/- alpha blockers>< 10mm shockwave lithotripsy +/- alpha blockers 10-20 mm ureteroscopy Further details https://www.passmedicine.com/v7/question/questions.php?q=0 3/7 4/6/24, 2:59 PM PassMedicine Stones < 5 mm will usually pass spontaneously. Lithotripsy and nephrolithotomy may be for severe cases. Most renal stones measuring less than 5mm in maximum diameter will typically pass within 4 weeks of symptom onset. More intensive and urgent treatment is indicated in the presence of ureteric obstruction, renal developmental abnormality such as horseshoe kidney and previous renal transplant. Ureteric obstruction due to stones together with infection is a surgical emergency and the system must be decompressed. Options include nephrostomy tube placement, insertion of ureteric catheters and ureteric stent placement. Shockwave lithotripsy A shock wave is generated external to the patient, internally cavitation bubbles and mechanical stress lead to stone fragmentation The passage of shock waves can result in the development of solid organ injury Fragmentation of larger stones may result in the development of ureteric obstruction The procedure is uncomfortable for patients and analgesia is required during the procedure and afterwards. Ureteroscopy A ureteroscope is passed retrograde through the ureter and into the renal pelvis It is indicated in individuals (e.g. pregnant females) where lithotripsy is contraindicated and in complex stone disease In most cases a stent is left in situ for 4 weeks after the procedure. Percutaneous nephrolithotomy In this procedure, access is gained to the renal collecting system Once access is achieved, intra corporeal lithotripsy or stone fragmentation is performed and stone fragments removed. Prevention of renal stones Calcium stones may be due to hypercalciuria, which is found in up to 5-10% of the general population. high fluid intake add lemon juice to drinking water avoid carbonated drinks limit salt intake potassium citrate may be beneficial NICE thiazides diuretics (increase distal tubular calcium resorption) https://www.passmedicine.com/v7/question/questions.php?q=0 4/7 4/6/24, 2:59 PM PassMedicine Oxalate stones cholestyramine reduces urinary oxalate secretion pyridoxine reduces urinary oxalate secretion Uric acid stones allopurinol urinary alkalinization e.g. oral bicarbonate Next question                Textbooks High-yield textbook Extended textbook Links Clinical Knowledge Summaries 4 0 6 9 Renal colic British Association of Urological Surgeons 3 0 A 9 2018 Renal colic guidelines NICE 6 0 9 0 2019 Renal and ureteric stones: assessment and management European Urology Association 6 3 9 1 https://www.passmedicine.com/v7/question/questions.php?q=0 5/7 4/6/24, 2:59 PM PassMedicine 2015 Urolithiasis guidelines British Journal of Urology 0 1 2015 Discussion regarding evidence base (or lack of it) for alpha blockers Royal College of Physicians 0 1 2012 Kidney stone disease: pathophysiology, investigation and medical treatment Report broken link Media Kidney stones Osmosis - YouTube 14 0 Urinary/Kidney Stones Armando Hasudungan - YouTube 5 1 Understanding Kidney Stones Zero To Finals - YouTube 5 1 Report broken media https://www.passmedicine.com/v7/question/questions.php?q=0 6/7 4/6/24, 3:00 PM PassMedicine PassMedicine Question 5 of 244 Which of the following factors would suggest that a patient has pre-renal uraemia rather than established acute tubular necrosis? Urine sodium = 70 mmol/L 19% Fractional urea excretion = 20% 43% No response to fluid challenge 7% Urine:plasma urea ratio 5:1 18% Specific gravity = 1005 13% ATN or prerenal uraemia? In prerenal uraemia think of the kidneys holding on to sodium to preserve volume Important for me Less important Discuss (13) Improve Next question Acute kidney injury: acute tubular necrosis vs. prerenal uraemia Pre-renal uraemia ('azotemia') Acute tubular necrosis Urine sodium < 20 mmol/L > 40 mmol/L Urine osmolality > 500 mOsm/kg < 350 mOsm/kg Fractional sodium excretion* < 1% > 1% Response to fluid challenge Good Poor https://www.passmedicine.com/v7/question/questions.php?q=0 1/4 4/6/24, 3:00 PM PassMedicine Pre-renal uraemia ('azotemia') Acute tubular necrosis Serum urea:creatinine ratio Raised Normal Fractional urea excretion** < 35% >35% Urine:plasma osmolality > 1.5 < 1.1 Urine:plasma urea > 10:1 < 8:1 Specific gravity > 1020 < 1010 Urine Normal/ 'bland' sediment Brown granular casts Prerenal uraemia - kidneys hold on to sodium to preserve volume *fractional sodium excretion = (urine sodium/plasma sodium) / (urine creatinine/plasma creatinine) x 100 **fractional urea excretion = (urine urea /blood urea ) / (urine creatinine/plasma creatinine) x 100 Next question                Textbooks High-yield textbook Extended textbook Links Think Kidneys https://www.passmedicine.com/v7/question/questions.php?q=0 2/4 4/6/24, 3:00 PM PassMedicine 4 2 Resources for doctors Royal College of Physicians 2 2 2012 Recognising acute kidney injury Report broken link Media Acute tubular necrosis Zero To Finals - YouTube 28 3 Prerenal acute kidney injury Osmosis - YouTube 35 4 Acute kidney injury Armando Hasudungan - YouTube 25 3 Intrarenal acute kidney injury Osmosis - YouTube 23 4 Report broken media https://www.passmedicine.com/v7/question/questions.php?q=0 3/4 4/6/24, 3:00 PM PassMedicine PassMedicine Question 6 of 244 A 33-year-old man with a history of coeliac disease is admitted for investigation of recurrent macroscopic haematuria. His urine is typically brown and there is no history of passing clots. What is the most likely diagnosis? Diffuse proliferative glomerulonephritis 12% IgA nephropathy 62% Membranous glomerulonephritis 16% Minimal change disease 3% Rapidly progressive glomerulonephritis 8% The correct answer is IgA nephropathy. IgA nephropathy, also known as Berger's disease, is the most common cause of glomerulonephritis worldwide. It is characterised by the deposition of immunoglobulin A (IgA) in the glomeruli leading to inflammation and damage. The classic presentation is episodic macroscopic haematuria, often following a mucosal infection such as an upper respiratory tract infection. However, it can also present with recurrent macroscopic haematuria without any precipitating factors. Coeliac disease has been linked with IgA nephropathy due to the shared pathophysiology of abnormal IgA immune responses. Diffuse proliferative glomerulonephritis typically presents with features of nephritic syndrome including haematuria, hypertension, oedema and renal impairment. It is most commonly associated with systemic lupus erythematosus (SLE), which doesn't match this patient's history. Membranous glomerulonephritis usually presents with nephrotic syndrome characterised by heavy proteinuria, hypoalbuminaemia leading to oedema, hyperlipidaemia and lipiduria. Haematuria can be seen but is not a prominent feature. Minimal change disease, despite being the most common cause of nephrotic syndrome in children, rarely causes haematuria. Its main presentation is sudden onset oedema due to massive proteinuria. Lastly, Rapidly progressive glomerulonephritis (RPGN) presents with rapidly deteriorating renal function over days to weeks with features of a nephritic syndrome including haematuria. However, RPGN would typically cause other systemic symptoms such as fever or malaise which are not https://www.passmedicine.com/v7/question/questions.php?q=0 1/5 4/6/24, 3:00 PM PassMedicine mentioned in this case. Discuss Improve Next question IgA nephropathy IgA nephropathy (also known as Berger's disease) is the commonest cause of glomerulonephritis worldwide. It classically presents as macroscopic haematuria in young people following an upper respiratory tract infection. Associated conditions alcoholic cirrhosis coeliac disease/dermatitis herpetiformis Henoch-Schonlein purpura Pathophysiology thought to be caused by mesangial deposition of IgA immune complexes there is considerable pathological overlap with Henoch-Schonlein purpura (HSP) histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3 Presentations young male, recurrent episodes of macroscopic haematuria typically associated with a recent respiratory tract infection nephrotic range proteinuria is rare renal failure is unusual and seen in a minority of patients Differentiating between IgA nephropathy and post-streptococcal glomerulonephritis post-streptococcal glomerulonephritis is associated with low complement levels main symptom in post-streptococcal glomerulonephritis is proteinuria (although haematuria can occur) there is typically an interval between URTI and the onset of renal problems in post- streptococcal glomerulonephritis https://www.passmedicine.com/v7/question/questions.php?q=0 2/5 4/6/24, 3:00 PM PassMedicine Management isolated hematuria, no or minimal proteinuria (less than 500 to 1000 mg/day), and a normal glomerular filtration rate (GFR) no treatment needed, other than follow-up to check renal function persistent proteinuria (above 500 to 1000 mg/day), a normal or only slightly reduced GFR initial treatment is with ACE inhibitors if there is active disease (e.g. falling GFR) or failure to respond to ACE inhibitors immunosuppression with corticosteroids Prognosis 25% of patients develop ESRF markers of good prognosis: frank haematuria markers of poor prognosis: male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidaemia, ACE genotype DD https://www.passmedicine.com/v7/question/questions.php?q=0 3/5 4/6/24, 3:00 PM PassMedicine Next question                Textbooks High-yield textbook Extended textbook Links Royal College of Physicians 7 1 2012 Evaluation and management of IgA nephropathy Journal of Royal College of Physicians of Edinburgh 2 1 What does STOP-IgAN tell us about how to treat IgA nephropathy? Report broken link Media IgA nephropathy Osmosis - YouTube 37 3 https://www.passmedicine.com/v7/question/questions.php?q=0 4/5 4/6/24, 3:00 PM PassMedicine PassMedicine Question 7 of 244 A 62-year-old man attends your clinic. He has a history of hypertension and atrial fibrillation for which he is anticoagulated with warfarin. A urine dipstick taken 8 weeks ago during a routine hypertension clinic appointment showed blood + with leucocytes +. Initial urine microscopy and culture shows no growth. The urine dipstick has been repeated on two further occasions with the same finding. What is the most appropriate action? Take no further action 25% Send a 24-urine sample for protein estimation 21% Refer to nephrology 24% Refer to urology 22% Send a further urine microscopy 8% The incidence of non-visible haematuria is similar in patients taking warfarin to the general population, therefore, these patients should be investigated as normal. Most haematuria protocols suggest sending younger patients (e.g. < 40 years) to nephrology initially but as this patient is older he should be sent to urology for a cystoscopy. Discuss (7) Improve Next question Haematuria The management of patients with haematuria is often difficult due to the absence of widely followed guidelines. It is sometimes unclear whether patients are best managed in primary care, by urologists or by nephrologists. https://www.passmedicine.com/v7/question/questions.php?q=0 1/4 4/6/24, 3:00 PM PassMedicine The terminology surrounding haematuria is changing. Microscopic or dipstick positive haematuria is increasingly termed non-visible haematuria whilst macroscopic haematuria is termed visible haematuria. Non-visible haematuria is found in around 2.5% of the population. Causes of transient or spurious non-visible haematuria urinary tract infection menstruation vigorous exercise (this normally settles after around 3 days) sexual intercourse Causes of persistent non-visible haematuria cancer (bladder, renal, prostate) stones benign prostatic hyperplasia prostatitis urethritis e.g. Chlamydia renal causes: IgA nephropathy, thin basement membrane disease Spurious causes - red/orange urine, where blood is not present on dipstick foods: beetroot, rhubarb drugs: rifampicin, doxorubicin Management Current evidence does not support screening for haematuria. The incidence of non-visible haematuria is similar in patients taking aspirin/warfarin to the general population hence these patients should also be investigated. Testing urine dipstick is the test of choice for detecting haematuria persistent non-visible haematuria is often defined as blood being present in 2 out of 3 samples tested 2-3 weeks apart renal function, albumin:creatinine (ACR) or protein:creatinine ratio (PCR) and blood pressure should also be checked urine microscopy may be used but time to analysis significantly affects the number of red blood cells detected NICE urgent cancer referral guidelines were updated in 2015. Urgent referral (i.e. within 2 weeks) https://www.passmedicine.com/v7/question/questions.php?q=0 2/4 4/6/24, 3:00 PM PassMedicine Aged >= 45 years AND: unexplained visible haematuria without urinary tract infection, or visible haematuria that persists or recurs after successful treatment of urinary tract infection Aged >= 60 years AND have unexplained nonvisible haematuria and either dysuria or a raised white cell count on a blood test Non-urgent referral Aged 60 >= 60 years with recurrent or persistent unexplained urinary tract infection Since the investigation (or not) of non-visible haematuria is such as a common dilemma a number of guidelines have been published. They generally agree with NICE guidance, of note: patients under the age of 40 years with normal renal function, no proteinuria and who are normotensive do not need to be referred and may be managed in primary care Next question                Textbooks High-yield textbook Extended textbook Links NICE 4 2 6 9 2015 Suspected cancer: recognition and referral Report broken link https://www.passmedicine.com/v7/question/questions.php?q=0 3/4 4/6/24, 3:01 PM PassMedicine PassMedicine Question 8 of 244 A 40-year-old woman presents to her GP, anxious to be 'checked out' because her older brother recently passed away from a haemorrhagic stroke. She was told that his autopsy showed cerebral aneurysmal rupture. The patient is well currently, with no fever, weight loss, headache or dysuria but has been treated for recurrent urinary tract infections (UTIs) over the past 3 years. Her father had a history of chronic kidney disease (CKD) and passed away from a stroke at age 65. What is the most appropriate investigation for diagnosis of this patient's condition? Computed tomography (CT) scan of the abdomen with contrast 6% Cranial magnetic resonance angiography 3% Kidneys, ureters and bladder (KUB) X-ray 3% Molecular genetic testing 6% Renal ultrasound scan (USS) 81% Ultrasound is the screening test for adult polycystic kidney disease Important for me Less important Given the patient's personal and family history, she has an increased risk of autosomal dominant polycystic kidney disease (ADPKD), the most common genetic cause of CKD. Mutations of PKD1/PKD2 genes lead to cystic degeneration of renal parenchyma, resulting in enlargement of the kidneys, hypertension, recurrent UTIs, haematuria and flank pain. ADPKD is also associated with extrarenal manifestations such as pancreatic/hepatic cysts, mitral valve prolapse, aortic regurgitation and intracranial aneurysms (a cause of haemorrhagic stroke). Renal ultrasound (USS) is the preferred screening modality as age-dependent diagnostic criteria have high sensitivity and specificity and because of its low cost, no exposure to radiation and widespread availability. CT scan of the abdomen can diagnose ADPKD but is inappropriate for screening, considering USS is a relatively cheaper, safer and more widely available option. This patient needs screening for ADPKD and has no signs of an intracranial aneurysm (e.g. headache). Considering her strong family history of ADPKD-associated intracranial aneurysms she https://www.passmedicine.com/v7/question/questions.php?q=0 1/5 4/6/24, 3:01 PM PassMedicine may benefit from aneurysmal screening if she ever develops a headache or neurological symptoms, using cranial magnetic resonance angiography. A KUB X-ray cannot detect polycystic kidneys. However, it is used commonly as the first-line investigation for urolithiasis. Genetic testing is less cost-efficient than USS. It is also not a useful screening tool for ADPKD since current genotypic testing can only identify approximately 70% of the known pathogenic intragenic PKD1 and PKD2 mutations. Discuss (2) Improve Next question ADPKD Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians. Two disease loci have been identified, PKD1 and PKD2, which code for polycystin-1 and polycystin-2 respectively ADPKD type 1 ADPKD type 2 85% of cases 15% of cases Chromosome 16 Chromosome 4 Presents with renal failure earlier The screening investigation for relatives is abdominal ultrasound: Ultrasound diagnostic criteria (in patients with positive family history) two cysts, unilateral or bilateral, if aged < 30 years two cysts in both kidneys if aged 30-59 years four cysts in both kidneys if aged > 60 years Management For select patients, tolvaptan (vasopressin receptor 2 antagonist) may be an option. NICE https://www.passmedicine.com/v7/question/questions.php?q=0 2/5 4/6/24, 3:01 PM PassMedicine recommended it as an option for treating ADPKD in adults to slow the progression of cyst development and renal insufficiency only if: they have chronic kidney disease stage 2 or 3 at the start of treatment there is evidence of rapidly progressing disease and the company provides it with the discount agreed in the patient access scheme. © Image used on license from PathoPic Extensive cysts are seen in an enlarged kidney Next question                Textbooks High-yield textbook Extended textbook https://www.passmedicine.com/v7/question/questions.php?q=0 3/5 4/6/24, 3:01 PM PassMedicine Media Polycystic Kidney Disease Explained Rhesus Medicine - YouTube 8 0 Polycystic kidney disease Osmosis - YouTube 23 5 Autosomal dominant polycystic kidney disease Armando Hasudungan - YouTube 17 7 Report broken media Score: 12.5% 1 2 3 4 5 6 7 8 https://www.passmedicine.com/v7/question/questions.php?q=0 4/5 4/6/24, 3:01 PM PassMedicine PassMedicine Question 9 of 244 An 18-year-old man presents to the Nephrology clinic for review, after describing ongoing frothy urine. He has no significant past medical history and is otherwise well in himself. In the clinic, his observations are as follows: blood pressure 118/68 mmHg, heart rate 80/min, respiratory rate 14/min, oxygen saturation 97% on air, temperature 36.7ºC. The results of recent investigations are shown below: 24h urinary protein collection 4.2g 3.5g/24h. As he is a young adult with no obvious regular medications or medical comorbidities to provoke nephrotic syndrome, the most likely diagnosis is minimal change glomerulonephritis. This diagnosis is clinched by the classic findings of podocyte fusion and effacement of the podocyte foot processes on renal biopsy. As around 80% of cases of minimal change disease are steroid responsive, he should be given a corticosteroid. Of these, the preferred initial option for minimal change disease is prednisolone. https://www.passmedicine.com/v7/question/questions.php?q=0 1/4 4/6/24, 3:01 PM PassMedicine Cyclophosphamide is incorrect. This would be an appropriate agent for patients with minimal change disease who have not responded to an initial trial of prednisolone. Cyclophosphamide + methylprednisolone is incorrect. This is an intense immunosuppressive regime sometimes given to control membranous glomerulonephritis. It is not the first-line treatment for steroid-naïve patients with minimal change disease. Methylprednisolone is incorrect. Pulsed methylprednisolone may be given to achieve disease control in more rapidly progressive glomerulonephritides. In minimal change disease, less intensive treatment with oral prednisolone is preferred initially, due to the high likelihood of clinical response. Observation only is incorrect. Due to the high steroid-responsiveness of minimal change disease in most patients, it would be inappropriate to deny this patient treatment with steroids, and risk progression to more enduring renal failure. Discuss (5) Improve Next question Minimal change disease Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults. The majority of cases are idiopathic, but in around 10-20% a cause is found: drugs: NSAIDs, rifampicin Hodgkin's lymphoma, thymoma infectious mononucleosis Pathophysiology T-cell and cytokine-mediated damage to the glomerular basement membrane → polyanion loss the resultant reduction of electrostatic charge → increased glomerular permeability to serum albumin Features nephrotic syndrome normotension - hypertension is rare https://www.passmedicine.com/v7/question/questions.php?q=0 2/4 4/6/24, 3:01 PM PassMedicine highly selective proteinuria only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus renal biopsy normal glomeruli on light microscopy electron microscopy shows fusion of podocytes and effacement of foot processes Management oral corticosteroids: majority of cases (80%) are steroid-responsive cyclophosphamide is the next step for steroid-resistant cases Prognosis is overall good, although relapse is common. Roughly: 1/3 have just one episode 1/3 have infrequent relapses 1/3 have frequent relapses which stop before adulthood Next question                Textbooks High-yield textbook Extended textbook Media Minimal change disease Osmosis - YouTube 40 3 https://www.passmedicine.com/v7/question/questions.php?q=0 3/4 4/6/24, 3:02 PM PassMedicine PassMedicine Question 10 of 244 A 31-year-old man presents to his GP with a 2-month history of constant abdominal pain and early satiety. He has hypertension for which he takes enalapril. On examination, he is mildly tender in both flanks. Well-circumscribed masses are palpable in both left and right flanks. A soft systolic murmur is heard loudest at the apex. His observations are heart rate 67/min, blood pressure 152/94mmHg, temperature 37.2ºC, respiratory rate 14/min, saturations 97%. Which additional feature is most likely to be found in this patient? Hepatomegaly 52% Colonic polyps 9% Sensorineural deafness 21% Angiofibromas 15% Thrombocytopenia 3% ADPKD is associated with hepatomegaly (due to hepatic cysts) Important for me Less important The patient in this case has autosomal-dominant polycystic kidney disease (ADPKD). ADPKD often presents with abdominal pain and early satiety as the kidneys occupy a large volume of the abdomen. Traction on the kidney pedicle can also cause pain. The presence of hypertension, bilateral flank masses and a systolic apical murmur (suggesting mitral valve disease) also point towards this diagnosis. Extra-renal features of ADPKD include: Hepatic cysts which manifest as hepatomegaly Diverticulosis Intracranial aneurysms Ovarian cysts https://www.passmedicine.com/v7/question/questions.php?q=0 1/4 4/6/24, 3:02 PM PassMedicine Colonic polyps are not a feature of ADPKD. Angiofibromas are a feature of tuberous sclerosis (patients with this disease may have renal cysts). Tuberous sclerosis is usually diagnosed in childhood and is associated with epilepsy and cognitive impairment. Sensorineural deafness is associated with Alport's syndrome. Alport's syndrome typically presents with haematuria and progressive renal failure, not renal enlargement. Thrombocytopenia is not a feature of ADPKD. Discuss (6) Improve Next question ADPKD: features Features hypertension recurrent UTIs flank pain haematuria palpable kidneys renal impairment renal stones Extra-renal manifestations liver cysts (70% - the commonest extra-renal manifestation): may cause hepatomegaly berry aneurysms (8%): rupture can cause subarachnoid haemorrhage cardiovascular system: mitral valve prolapse, mitral/tricuspid incompetence, aortic root dilation, aortic dissection cysts in other organs: pancreas, spleen; very rarely: thyroid, oesophagus, ovary https://www.passmedicine.com/v7/question/questions.php?q=0 2/4 4/6/24, 3:02 PM PassMedicine Next question                Textbooks High-yield textbook Extended textbook Media https://www.passmedicine.com/v7/question/questions.php?q=0 3/4 4/6/24, 3:02 PM PassMedicine PassMedicine Question 11 of 244 Which one of the following factors is most associated with an increased risk of developing bladder cancer? Strongyloides stercoralis infection 8% Beryllium salt exposure 3% Aniline dye exposure 77% Aflatoxin exposure 8% Long term phenytoin use 3% The correct answer is Aniline dye exposure. Aniline dyes are aromatic amines used in various industries such as the rubber, chemical, textile and leather industries. Numerous studies have shown a strong association between exposure to aniline dyes and an increased risk of developing bladder cancer. The International Agency for Research on Cancer (IARC) has classified some aromatic amines including benzidine and 2-naphthylamine, which are types of aniline dyes, as Group 1 carcinogens, meaning there is sufficient evidence of their carcinogenicity in humans. Strongyloides stercoralis infection is not typically associated with bladder cancer. This parasitic infection primarily affects the intestines and can cause abdominal pain, diarrhoea, and rash. In severe cases or in immunocompromised individuals, it can lead to hyperinfection syndrome or disseminated disease affecting multiple organs but it does not increase the risk of bladder cancer. Beryllium salt exposure has been linked to lung disease and lung cancer but there's no significant evidence associating it with bladder cancer. Beryllium is a metal used in various industries such as aerospace, nuclear weapons production, electronics and dental appliances manufacturing. Chronic beryllium disease (CBD), a granulomatous lung disorder caused by inhalation of beryllium particles or fumes, can lead to pulmonary fibrosis but not bladder cancer. Exposure to Aflatoxin, a mycotoxin produced by the fungi Aspergillus flavus and Aspergillus parasiticus, has been strongly associated with liver cancer but not bladder cancer. Aflatoxin contamination often occurs in crops like peanuts, maize and cottonseed that are stored in warm humid conditions conducive for fungal growth. Lastly, long-term use of the antiepileptic drug Phenytoin has been associated with several side https://www.passmedicine.com/v7/question/questions.php?q=0 1/3 4/6/24, 3:02 PM PassMedicine effects including gingival hyperplasia, hirsutism, folate deficiency and osteomalacia but there's no established link between phenytoin use and increased risk of bladder cancer. Phenytoin may induce chronic liver disease due to its hepatic metabolism which could potentially increase the risk of hepatocellular carcinoma but this association remains controversial. 6 Q 0 Discuss (4) Improve Next question Bladder cancer: risk factors Risk factors for urothelial (transitional cell) carcinoma of the bladder include: Smoking o most important risk factor in western countries o hazard ratio is around 4 Exposure to aniline dyes o for example working in the printing and textile industry o examples are 2-naphthylamine and benzidine Rubber manufacture Cyclophosphamide Risk factors for squamous cell carcinoma of the bladder include: Schistosomiasis Smoking Next question                Textbooks High-yield textbook https://www.passmedicine.com/v7/question/questions.php?q=0 2/3 4/6/24, 3:03 PM PassMedicine PassMedicine Question 12 of 244 Autosomal dominant polycystic kidney disease type 2 is associated with a gene defect in: Chromosome 4 61% Chromosome 8 6% Chromosome 12 5% Chromosome 16 26% Chromosome 20 1% ADPKD type 2 = chromosome 4 = 15% of cases Important for me Less important The correct answer is Chromosome 4. Autosomal dominant polycystic kidney disease (ADPKD) type 2 is associated with mutations in the PKD2 gene, which is located on chromosome 4. This gene codes for a protein called polycystin-2, which appears to be involved in regulating cell division and preventing the formation of cysts. Mutations in this gene can disrupt these functions and lead to the development of ADPKD. Chromosome 8 is incorrect as it is not associated with ADPKD. However, it should be noted that chromosome 8 has been linked to other diseases such as Burkitt's lymphoma, where translocation between chromosomes 8 and 14 occurs leading to overexpression of the c-myc oncogene. Chromosome 12 is also incorrect. There are no known associations between ADPKD and chromosome 12. Nevertheless, mutations on this chromosome have been implicated in several other conditions including hypochondroplasia and some forms of colorectal cancer. Chromosome 16, while incorrect for ADPKD type 2, is important for another form of the disease - ADPKD type 1. The PKD1 gene located on this chromosome encodes polycystin-1, another protein involved in cell signalling and adhesion. Mutations here can give rise to this more common form of ADPKD. Finally, Chromosome 20 does not harbour any genes known to be related to either form of https://www.passmedicine.com/v7/question/questions.php?q=0 1/4 4/6/24, 3:03 PM PassMedicine ADPKD. Nonetheless, it carries genes associated with other disorders such as Alagille syndrome and Creutzfeldt-Jakob disease. Discuss (2) Improve Next question ADPKD Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians. Two disease loci have been identified, PKD1 and PKD2, which code for polycystin-1 and polycystin-2 respectively ADPKD type 1 ADPKD type 2 85% of cases 15% of cases Chromosome 16 Chromosome 4 Presents with renal failure earlier The screening investigation for relatives is abdominal ultrasound: Ultrasound diagnostic criteria (in patients with positive family history) two cysts, unilateral or bilateral, if aged < 30 years two cysts in both kidneys if aged 30-59 years four cysts in both kidneys if aged > 60 years Management For select patients, tolvaptan (vasopressin receptor 2 antagonist) may be an option. NICE recommended it as an option for treating ADPKD in adults to slow the progression of cyst development and renal insufficiency only if: they have chronic kidney disease stage 2 or 3 at the start of treatment there is evidence of rapidly progressing disease and the company provides it with the discount agreed in the patient access scheme. https://www.passmedicine.com/v7/question/questions.php?q=0 2/4 4/6/24, 3:03 PM PassMedicine © Image used on license from PathoPic Extensive cysts are seen in an enlarged kidney Next question                Textbooks High-yield textbook Extended textbook Media https://www.passmedicine.com/v7/question/questions.php?q=0 3/4 4/6/24, 3:03 PM PassMedicine PassMedicine Question 13 of 244 A 45-year-old man is seen in the Nephrology clinic after an abnormality was identified in some routine blood tests taken by his GP. He has no significant past medical history, and does not take any regular medications. On examination, the only abnormality is moderate peripheral oedema extending to the knees bilaterally. His investigation results are as follows: Male: (135-180) Hb 140 g/L Female: (115 - 160) Platelets 335 * 109/L (150 - 400) WBC 6.8 * 109/L (4.0 - 11.0) Na+ 138 mmol/L (135 - 145) K+ 4.8 mmol/L (3.5 - 5.0) Urea 11.2 mmol/L (2.0 - 7.0) Creatinine 158 µmol/L (55 - 120) CRP 5 mg/L (< 5) Albumin 25 g/L (35 - 50) 24h urinary protein collection 4.2g Renal 'The basement membrane is thickened with subepithelial electron dense deposits, creating a biopsy: 'spike and dome' appearance.' Which of the following antibodies is most likely to be positive in this patient? Anti-liver-kidney microsomal type 2 antibodies 4% Anti-phospholipase A2 antibodies 87% Anti-p62 antibodies 1% Anti-Ri antibodies 2% Anti-GQ1b antibodies 5% https://www.passmedicine.com/v7/question/questions.php?q=0 1/5 4/6/24, 3:03 PM PassMedicine Idiopathic membranous glomerulonephritis is related to anti-phospholipase A2 antibodies Important for me Less important This patient has presented with nephrotic syndrome, as evidenced by hypoalbuminaemia, renal impairment, and nephrotic range proteinuria (> 3.5g/24h). Of the diseases leading to nephrotic syndrome, the most likely culprit is membranous glomerulonephritis (GN). This is supported by a first presentation during adulthood (minimal change disease most commonly first presents during childhood), and the classic pathological findings of a 'spike and dome' appearance of the basement membrane due to subepithelial deposits. The pathological findings for minimal change disease are often only a subtle effacement of the podocytes, whilst focal segmental glomerular sclerosis (FSGS) would give foci of sclerosed glomeruli! The absence of precipitants for membranous GN in the history, such as culprit drugs like NSAIDs, recent infections or a history consistent with malignancy make idiopathic membranous GN the most likely diagnosis. Idiopathic membranous GN is associated with anti-phospholipase A2 antibodies. Anti-liver-kidney microsomal type 2 antibodies are associated with drug-induced hepatitis (whereas anti-LKM type 1 antibodies are associated with autoimmune hepatitis). Anti-p62 antibodies are associated with primary biliary cirrhosis. Anti-Ri antibodies are associated with opsoclonus-myoclonus syndrome, often in the context of breast cancer. Anti-GQ1b antibodies are associated with Miller-Fisher syndrome, a variant of Guillain-Barre syndrome characterised by ataxia, ophthalmoplegia and areflexia. Discuss (2) Improve Next question Membranous glomerulonephritis Membranous glomerulonephritis is the commonest type of glomerulonephritis in adults and is the third most common cause of end-stage renal failure (ESRF). It usually presents with nephrotic syndrome or proteinuria. Renal biopsy demonstrates: electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. This creates a 'spike and dome' appearance https://www.passmedicine.com/v7/question/questions.php?q=0 2/5 4/6/24, 3:03 PM PassMedicine Causes idiopathic: due to anti-phospholipase A2 antibodies infections: hepatitis B, malaria, syphilis malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia drugs: gold, penicillamine, NSAIDs autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid Management all patients should receive an ACE inhibitor or an angiotensin II receptor blocker (ARB): these have been shown to reduce proteinuria and improve prognosis immunosuppression as many patients spontaneously improve only patient with severe or progressive disease require immunosuppression corticosteroids alone have not been shown to be effective. A combination of corticosteroid + another agent such as cyclophosphamide is often used consider anticoagulation for high-risk patients Prognosis - rule of thirds one-third: spontaneous remission one-third: remain proteinuric one-third: develop ESRF Good prognostic features include female sex, young age at presentation and asymptomatic proteinuria of a modest degree at the time of presentation. Next question                https://www.passmedicine.com/v7/question/questions.php?q=0 3/5 4/6/24, 3:03 PM PassMedicine Textbooks High-yield textbook Extended textbook Links American Society of Nephrology 8 4 2017 Primary Membranous Nephropathy review Royal College of Physicians 4 5 2012 Membranous nephropathy review Report broken link Media Membranous glomerulonephritis (membranous nephropathy) Osmosis - YouTube 39 7 Report broken media Score: 7.7% 1 2 3 4 5 https://www.passmedicine.com/v7/question/questions.php?q=0 4/5 4/6/24, 3:04 PM PassMedicine PassMedicine Question 14 of 244 A 54-year-old man presents to the emergency department having felt generally unwell over the last week. On review, he is oliguric and hypertensive and his urine dip is positive for blood and protein. His past medical history includes hypertension and recurrent sinusitis. His blood results are below. Na+ 144 mmol/L (135 - 145) K+ 5.9 mmol/L (3.5 - 5.0) Urea 12.6 mmol/L (2.0 - 7.0) Creatinine 436 µmol/L (55 - 120) What is the most likely underlying diagnosis? Eosinophilic granulomatosis with polyangiitis 18% Goodpasture's syndrome 9% Granulomatosis with polyangiitis 62% IgA nephropathy 10% Systemic lupus erythematosus (SLE) 1% The presence of upper respiratory tract signs points towards granulomatosis with polyangiitis in a patient with rapidly progressive glomerulonephritis Important for me Less important This patient has a presentation consistent with rapidly progressive glomerulonephritis (RPGN). He has been unwell for a short period of time and has an extremely high creatinine, with no prior diagnosis of CKD. His presentation is consistent with a nephritic syndrome, which would be expected. The history of recurrent sinusitis points to granulomatosis with polyangiitis as the most likely cause. Other suggestive features might be epistaxis or a saddle-shaped nose. Eosinophilic granulomatosis with polyangiitis is less associated with RPGN. It is also more associated with lower respiratory tract symptoms, e.g. a recent diagnosis of asthma, and you may see eosinophilia on blood tests. https://www.passmedicine.com/v7/question/questions.php?q=0 1/5 4/6/24, 3:04 PM PassMedicine SLE is a cause of RPGN. However, there are no specific symptoms that hint towards this diagnosis. A younger female would also be a more typical demographic for the first presentation of SLE. Goodpasture's syndrome can cause RPGN. It typically affects those aged 20-30 and 60-70. However, the specific feature of sinusitis points away from this diagnosis. Pulmonary haemorrhages would be more classical of Goodpasture's. IgA nephropathy can cause RPGN, but this is not a typical presentation of that diagnosis. You would expect a young patient to present just after an acute upper respiratory tract infection with macroscopic haematuria. Discuss (2) Improve Next question Rapidly progressive glomerulonephritis Rapidly progressive glomerulonephritis is a term used to describe a rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli. Causes Goodpasture's syndrome Wegener's granulomatosis others: SLE, microscopic polyarteritis Features nephritic syndrome: haematuria with red cell casts, proteinuria, hypertension, oliguria features specific to underlying cause (e.g. haemoptysis with Goodpasture's, vasculitic rash or sinusitis with Wegener's) https://www.passmedicine.com/v7/question/questions.php?q=0 2/5 4/6/24, 3:04 PM PassMedicine © Image used on license from PathoPic Glomeruli are full of crescents. © Image used on license from PathoPic Another image showing the glomeruli full of crescents Next question                https://www.passmedicine.com/v7/question/questions.php?q=0 3/5 4/6/24, 3:04 PM PassMedicine Textbooks High-yield textbook Extended textbook Media Rapidly progressive glomerulonephritis Osmosis - YouTube 31 0 Understanding Nephritic Syndrome (With Pathology Made Easy) Rhesus Medicine - YouTube 6 2 Report broken media Score: 7.1% 1 2 3 4 5 6 7 8 https://www.passmedicine.com/v7/question/questions.php?q=0 4/5 4/6/24, 3:04 PM PassMedicine PassMedicine Question 15 of 244 A 72-year-old man with a background of metastatic prostate cancer being managed conservatively attends his GP for a review of symptom control. Updated blood tests are performed. Urea 26.4 mmol/L (2.0 - 7.0) Creatinine 348 µmol/L (55 - 120) Renal function 3 months ago was normal. He has no family history of renal disease and takes no regular medications. A urine dip is performed which shows +++ protein. What is the most likely cause of this new renal impairment? Focal segmental glomerulosclerosis 14% Membranous glomerulonephritis 66% Minimal change disease 4% Renal papillary necrosis 10% Type 1 membranoproliferative glomerulonephritis 7% Membranous nephropathy is frequently associated with malignancy Important for me Less important Membranous glomerulonephritis often results from malignancy, including prostate cancer. The picture of rapidly progressing renal failure with proteinuria, without any other obvious cause (inherited or iatrogenic) suggests that membranous glomerulonephritis is most likely. Focal segmental glomerulosclerosis would cause proteinuria and renal failure but is not typically caused by malignancy and tends to present in young adults. https://www.passmedicine.com/v7/question/questions.php?q=0 1/5 4/6/24, 3:04 PM PassMedicine Minimal change disease is another cause of nephrotic syndrome but it is far less common in older adults and is not caused by prostate cancer. Causes include NSAIDs, Hodgkin's lymphoma and infectious mononucleosis. Renal papillary necrosis can cause proteinuria but would probably cause visible haematuria and possibly loin pain. It is not caused by malignancy. Typically it results from pyelonephritis, renal obstruction or NSAIDs. Type 1 membranoproliferative glomerulonephritis can present with proteinuria but is less common than membranous glomerulonephritis and is less commonly caused by malignancy. Causes include cryoglobulinemia (which is associated with haematological malignancy but not prostate cancer) and hepatitis C. Discuss (1) Improve Next question Membranous glomerulonephritis Membranous glomerulonephritis is the commonest type of glomerulonephritis in adults and is the third most common cause of end-stage renal failure (ESRF). It usually presents with nephrotic syndrome or proteinuria. Renal biopsy demonstrates: electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. This creates a 'spike and dome' appearance Causes idiopathic: due to anti-phospholipase A2 antibodies infections: hepatitis B, malaria, syphilis malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia drugs: gold, penicillamine, NSAIDs autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid Management all patients should receive an ACE inhibitor or an angiotensin II receptor blocker (ARB): these have been shown to reduce proteinuria and improve prognosis immunosuppression https://www.passmedicine.com/v7/question/questions.php?q=0 2/5 4/6/24, 3:04 PM PassMedicine as many patients spontaneously improve only patient with severe or progressive disease require immunosuppression corticosteroids alone have not been shown to be effective. A combination of corticosteroid + another agent such as cyclophosphamide is often used consider anticoagulation for high-risk patients Prognosis - rule of thirds one-third: spontaneous remission one-third: remain proteinuric one-third: develop ESRF Good prognostic features include female sex, young age at presentation and asymptomatic proteinuria of a modest degree at the time of presentation. Next question                Textbooks High-yield textbook Extended textbook Links American Society of Nephrology 8 4 https://www.passmedicine.com/v7/question/questions.php?q=0 3/5 4/6/24, 3:05 PM PassMedicine PassMedicine Question 16 of 244 A 49-year-old is admitted to hospital with an intensely painful lesion on the right leg. He has a background of end-stage renal failure, hypertension and atrial fibrillation. His regular medications include warfarin, amlodipine, ramipril and paracetamol. On examination, a painful, purpuric lesion is noted, with an area of black necrotic tissue. It appears to have ulcerated somewhat. A biopsy is taken which demonstrates calcium deposition in the lesion. What is the most likely diagnosis? Calciphylaxis 78% Cholesterol embolisation 4% Cryoglobulinaemia 3% Pyoderma gangrenosum 10% Warfarin necrosis 6% Calciphylaxis lesion are intensely painful, purpuric patches with an area of black necrotic tissue that may form bullae, ulcerate, and leave a hard, firm eschar Important for me Less important The description of the lesion points towards calciphylaxis, a rare complication of end-stage renal failure. It results in the deposition of calcium within arterioles, leading to microvascular occlusion and necrosis. Usually, it affects the skin (although can affect other organs), presenting as above with painful, purpuric lesions that necrose and may ulcerate. The skin biopsy demonstrating calcium deposition points more towards this diagnosis. Cholesterol embolisation may occur in patients on warfarin, although the history here is more suggestive of calciphylaxis. Release of cholesterol debris leads to emboli, which may create small, infarcted areas, with mottling and purple discolouration of extremities. Non-specific symptoms also include fever and muscle ache. Cryoglobulinaemia is the presence of cold-sensitive immunoglobulins that become insoluble at https://www.passmedicine.com/v7/question/questions.php?q=0 1/3 4/6/24, 3:05 PM PassMedicine reduced temperatures. This can present with purpura and acrocyanosis, but does not fit with the history here, given the presence of end-stage renal failure and calcium deposition in the lesion. Pyoderma gangrenosum is associated with a number of conditions, such as inflammatory bowel diseases, whereas calciphylaxis is more associated with end-stage renal failure. Pyoderma gangrenosum would instead present with an ulcerating, purple lesion that may have started as a small pustule or blister. A biopsy would demonstrate neutrophilic infiltration rather than calcium deposition. Warfarin necrosis is a reasonable differential here - a rare side effect of warfarin use. It presents with single or multiple necrotic lesions and may be difficult to differentiate clinically from calciphylaxis. However, the finding of calcium deposition on biopsy points towards calciphylaxis. å 9 0 Discuss Improve Next question Calciphylaxis Calciphylaxis is a rare complication of end-stage renal failure. The underlying mechanism is not clear, however it results in deposition of calcium within arterioles causing microvascular occlusion and necrosis of the supplied tissue. It most commonly affects the skin and presents with painful necrotic skin lesions. The risk of developing calciphylaxis is linked with hypercalcaemia, hyperphophataemia and hyperparathyroidism. Warfarin is widely reported as causing/exacerbating calciphylaxis in high risk patients, however the underlying mechanism is not known. Treatment of calciphylaxis focuses on reducing calcium and phosphate levels, controlling hyperparathyroidism and avoiding contributing drugs such as warfarin and calcium containing compounds. Next question                https://www.passmedicine.com/v7/question/questions.php?q=0 2/3 4/6/24, 3:05 PM PassMedicine PassMedicine Question 17 of 244 A 59-year-old man has a set of routine blood tests sent including renal function, which shows the following. Na+ 138 mmol/L (135 - 145) K+ 4.1 mmol/L (3.5 - 5.0) Bicarbonate 27 mmol/L (22 - 29) Urea 5.0 mmol/L (2.0 - 7.0) Creatinine 120 µmol/L (55 - 120) eGFR 65 ml/min (>90) His urine dip test is as follows: pH 6.0 Glucose Negative Ketones Negative Blood Negative Protein Negative Nitrite Negative Leukocytes Negative He has a renal ultrasound which shows no abnormalities. How would his renal function be classed? CKD stage 1 13% CKD stage 2 25% CKD stage 3a 3% CKD stage 3b 1% https://www.passmedicine.com/v7/question/questions.php?q=0 1/5 4/6/24, 3:05 PM PassMedicine Normal renal function 57% CKD: only diagnose stages 1 & 2 if supporting evidence to accompany eGFR Important for me Less important This patient has an eGFR of 65 ml/min. Patients should only be diagnosed with CKD stage 1 if eGFR >90ml/min or stage 2 if eGFR 60- 90ml/min if there are markers of kidney disease including proteinuria, haematuria, electrolyte abnormalities or structural abnormalities detected. This patient does not have any features of kidney damage making these answers incorrect. Hence this patient has a normal renal function. CKD stage 3a is diagnosed when a patient has an eGFR of 45-59 ml/min. CKD stage 3b is diagnosed when a patient has an eGFR of 30-44 ml/min. Discuss (4) Improve Next question Chronic kidney disease: eGFR and classification Serum creatinine may not provide an accurate estimate of renal function due to differences in muscle. For this reason, formulas were developed to help estimate the glomerular filtration rate (estimated GFR or eGFR). The most commonly used formula is the Modification of Diet in Renal Disease (MDRD) equation, which uses the following variables: serum creatinine age gender ethnicity Factors which may affect the result pregnancy muscle mass (e.g. amputees, body-builders) eating red meat 12 hours prior to the sample being taken https://www.passmedicine.com/v7/question/questions.php?q=0 2/5 4/6/24, 3:05 PM PassMedicine CKD may be classified according to GFR: CKD stage GFR range 1 Greater than 90 ml/min, with some sign of kidney damage on other tests (if all the kidney tests* are normal, there is no CKD) 2 60-90 ml/min with some sign of kidney damage (if kidney tests* are normal, there is no CKD) 3a 45-59 ml/min, a moderate reduction in kidney function 3b 30-44 ml/min, a moderate reduction in kidney function 4 15-29 ml/min, a severe reduction in kidney function 5 Less than 15 ml/min, established kidney failure - dialysis or a kidney transplant may be needed *i.e. normal U&Es and no proteinuria Next question                Textbooks High-yield textbook Extended textbook Links NICE 4 5 A 9 https://www.passmedicine.com/v7/question/questions.php?q=0 3/5 4/6/24, 3:06 PM PassMedicine PassMedicine Question 18 of 244 A 79-year-old complains of lower urinary tract symptoms. Which one of the following statements regarding benign prostatic hyperplasia is incorrect? Goserelin is licensed for refractory cases 40% Side-effects of 5 alpha-reductase inhibitors include ejaculation disorders and 12% gynaecomastia Possible presentations include recurrent urinary tract infection 5% 5 alpha-reductase inhibitors typically decrease the prostate specific antigen level 27% More common in black men 16% Goserelin (Zoladex) is not used in the management of benign prostatic hyperplasia Discuss (2) Improve Next question Benign prostatic hyperplasia Benign prostatic hyperplasia (BPH) is a common condition seen in older men. Risk factors age around 50% of 50-year-old men will have evidence of BPH and 30% will have symptoms around 80% of 80-year-old men have evidence of BPH ethnicity: black > white > Asian BPH typically presents with lower urinary tract symptoms (LUTS), which may be categorised into: voiding symptoms (obstructive): weak or intermittent urinary flow straining https://www.passmedicine.com/v7/question/questions.php?q=0 1/4 4/6/24, 3:06 PM PassMedicine hesitancy terminal dribbling incomplete emptying storage symptoms (irritative) urgency frequency urgency incontinence nocturia post-micturition dribbling complications urinary tract infection retention obstructive uropathy Assessment dipstick urine U&Es: particularly if chronic retention is suspected PSA: should be done if there are any obstructive symptoms, of if the patient is worried about prostate cancer urinary frequency-volume chart should be done for at least 3 days International Prostate Symptom Score (IPSS) tool for classifying the severity of lower urinary tract symptoms (LUTS) and assessing the impact of LUTS on quality of life Score 20-35: severely symptomatic Score 8-19: moderately symptomatic Score 0-7: mildly symptomatic Management options watchful waiting alpha-1 antagonists e.g. tamsulosin, alfuzosin decrease smooth muscle tone of the prostate and bladder considered first-line: NICE recommend if moderate-to-severe voiding symptoms (IPSS ≥ 8) improve symptoms in around 70% of men adverse effects: dizziness, postural hypotension, dry mouth, depression 5 alpha-reductase inhibitors e.g. finasteride block the conversion of testosterone to dihydrotestosterone (DHT), which is known to induce BPH indicated if the patient has a significantly enlarged prostate and is considered to be at high risk of progression https://www.passmedicine.com/v7/question/questions.php?q=0 2/4 4/6/24, 3:06 PM PassMedicine o unlike alpha-1 antagonists causes a reduction in prostate volume and hence may slow disease progression. This however takes time and symptoms may not improve for 6 months o may also decrease PSA concentrations by up to 50% o adverse effects: erectile dysfunction, reduced libido, ejaculation problems, gynaecomastia the use of combination therapy (alpha-1 antagonist + 5 alpha-reductase inhibitor) was supported by the Medical Therapy Of Prostatic Symptoms (MTOPS) trial and is also supported by NICE: 'If the man has bothersome moderate-to-severe voiding symptoms and prostatic enlargement' if there is a mixture of storage symptoms and voiding symptoms that persist after treatment with an alpha-blocker alone, then an antimuscarinic (anticholinergic) drug such as tolterodine or darifenacin may be tried surgery o transurethral resection of prostate (TURP) Next question                Textbooks High-yield textbook Extended textbook Links NICE 8 3 £ 9 2010 The management of lower urinary tract symptoms in men Clinical Knowledge Summaries 3 2 £ 9 Lower urinary tract symptoms in men Report broken link https://www.passmedicine.com/v7/question/questions.php?q=0 3/4 4/6/24, 3:06 PM PassMedicine PassMedicine