Renal Flashcards

Question

Autosomal Recessive Polycystic Kidney Disease (ARPKD): -common? -chromosome?

Answer 1

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is much less common than autosomal dominant disease (ADPKD). It is due to a defect in a gene located on chromosome 6

Answer 2

Diagnosis may be made on prenatal ultrasound or in early infancy with abdominal masses and renal failure. End-stage renal failure develops in childhood. Patients also typically have liver involvement, for example portal and interlobular fibrosis

Answer 3

Nephrotic 1. Proteinuria (> 3g/24hr) causing 2. Hypoalbuminemia (< 30g/L) and 3. Edema Nephritic: haematuria, hypertension

Answer 4

Loss of antithrombin-III (↑↑↑), proteins C and S and associated rise in fibrinogen levels predispose to thrombosis. Loss of TBG lowers total, but not free thyroxin levels

Answer 5

1. Glomerulonephritis (GN, c. 80%) • Minimal change GN (causes 75% in children, 25% in adults) • Membranous GN • Focal Segmental GlomeruloSclerosis 2. Systemic disease (c. 20%) • Amyloidosis • SLE 3. Drugs • Gold (sodium aurothiomalate), penicillamine 4. Others • Congenital • Neoplasia: carcinoma, lymphoma, leukemia, myeloma • Infection: bacterial endocarditis, hepatitis B, malaria • Renal vein thrombosis

Answer 6

• ↑ risk of infection due to urinary immunoglobulin loss • ↑ risk of thromboembolism related to loss of antithrombin III and plasminogen in the urine • Hyperlipidemia • Hypocalcemia (vitamin D and binding protein lost in urine) • Acute renal failure could be due to thrombotic renal veins it comes with lion pain and hematuria.

Answer 7

Membranous glomerulonephritis

Answer 8

IgA nephropathy - AKA Berger's disease, mesangioproliferative GN

Answer 9

3. Diffuse proliferative glomerulonephritis

Answer 10

4. Minimal change disease

Answer 11

5. Focal segmental glomerulosclerosis

Answer 12

6. Rapidly progressive glomerulonephritis (RPGN) - AKA Crescentic Glomerulonephritis

Answer 13

7. Mesangiocapillary glomerulonephritis (membranoproliferative)

Answer 14

• Post-streptococcal glomerulonephritis • Subacute bacterial endocarditis • Systemic lupus erythematosus • Mesangiocapillary glomerulonephritis

Answer 15

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 as nephrotic syndrome or proteinuria

Answer 16

Renal biopsy demonstrates: • Sub-epithelial immune complex (mainly IgG and C3) deposition in the glomerulus • Electron microscopy: the basement membrane is thickened with sub-epithelial electron dense deposits (IgG, C3)

Answer 17

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

Answer 18

Prognosis - rule of thirds • One-third: spontaneous remission • One-third: remain proteinuric • One-third: develop ESRF

Answer 19

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

Answer 20

• Also called Berger's disease or mesangioproliferative glomerulonephritis • Commonest cause of glomerulonephritis worldwide • Pathogenesis unknown, ?Mesangial deposition of IgA immune complexes • Histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3

Answer 21

• Post-streptococcal glomerulonephritis is associated with low complement levels • Main symptom in post-streptococcal glomerulonephritis is proteinuria (although hematuria can occur) • There is typically an interval between URTI and the onset of renal problems in post- streptococcal glomerulonephritis

Answer 22

• Young ♂, recurrent episodes of Hematuria, usually painless (sometimes with no renal impairment) • Typically associated with mucosal infections e.g., URTI • Nephrotic range proteinuria is rare, presents as nephritic syndrome • Renal failure

Answer 23

Associated conditions • Alcoholic cirrhosis • Celiac disease/dermatitis herpetiformis

Answer 24

Management • Steroids/immunosuppressants have not shown to be useful

Answer 25

• 25% of patients develop ESRF • Markers of good prognosis: frank hematuria • Markers of poor prognosis: ♂ gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidemia, ACE genotype DD

Answer 26

Minimal Change Glomerulonephritis nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults

Answer 27

Causes: majority of cases are idiopathic, but in around 10-20% a cause is found: • Drugs: NSAIDs, rifampicin • Hodgkin's lymphoma, NHL and thymoma • Infectious mononucleosis

Answer 28

Features • Nephrotic syndrome • Normotension - hypertension is rare • Hematuria is very rare • Highly selective proteinuria* (*only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus) • Renal biopsy: electron microscopy shows fusion of podocytes

Answer 29

Podocyte fusion is seen in minimal change glomerulonephritis but may occasionally be a feature of focal segmental glomerulosclerosis as well. Minimal change however is far more common

Answer 30

Management • Majority of cases (80%) are steroid responsive (prednisolone) • Cyclophosphamide is the next step for steroid resistant cases ACE inhibitors may be used to ↓ proteinuria in patients with heavy proteinuria or who have a slow response to prednisolone

Answer 31

Prognosis is overall good, although relapse is common. Roughly: • 1/3 have just one episode • 2/3 have relapses: o 1/3 have infrequent relapses o 1/3 have frequent relapses which stop before adulthood

Answer 32

• AKA membranoproliferative glomerulonephritis • Mixed nephritic/nephrotic presentation • Poor prognosis

Answer 33

Type 1: • Subendothelial immune deposits • Cause: Cryoglobulinemia (with low C4), hepatitis C Type 2 'dense deposit disease': • Intramembranous deposits of electron dense material • Causes: partial lipodystrophy, factor H deficiency • ↓ serum complement • C3b nephritic factor (an antibody against C3bbb) found in 70% (low C3) Type 3 • Causes: hepatitis B and C

Answer 34

Management • Steroids may be effective

Answer 35

nephrotic syndrome Causes • Idiopathic • Secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy • HIV • Heroin • Alport's syndrome • Sickle-cell Focal segmental glomerulosclerosis is noted for having a high recurrence rate in renal transplants

Answer 36

Alport's Syndrome is usually inherited in an X-linked dominant pattern*. It is due to a defect in the gene which codes for type IV collagen resulting in an abnormal glomerular-basement membrane (GBM). The disease is more severe in ♂s with ♀s rarely developing renal failure *in around 85% of cases - 10-15% of cases are inherited in an autosomal recessive fashion with rare autosomal dominant variants existing

Answer 37

Risk factors • Dehydration • Hypercalciuria, hyperparathyroidism, hypercalcemia • Cystinuria NOT CYSTINOSIS • High dietary oxalate • Renal tubular acidosis • Medullary sponge kidney, polycystic kidney disease • Beryllium or cadmium exposure

Answer 38

Risk factors for urate stones • Gout • Ileostomy: loss of bicarbonate and fluid results in acidic urine, causing the precipitation of uric acid

Answer 39

Drug causes • Drugs that promote calcium stones: loop diuretics, steroids, acetazolamide, theophylline • Thiazides can prevent calcium stones (↑ distal tubular calcium resorption)

Answer 40

Calcium oxalate, 40%, Opaque Mixed calcium oxalate/phosphate stones, 25%, Opaque Triple phosphate stones, 10%, Opaque Calcium phosphate, 10%, Opaque Urate stones, 5-10%, Radio-lucent Cystine stones 1% Semi-opaque, 'ground-glass' appearance Xanthine stones, <1%, Radio-lucent

Answer 41

stag-horn calculi involve the renal pelvis and extend into at least 2 calyces. They develop in alkaline urine and are composed of struvite (ammonium magnesium phosphate, triple phosphate). Ureaplasma urealyticum and Proteus infections predispose to their formation

Answer 42

Acute management of renal colic Diclofenac 75 mg by intramuscular injection is the analgesia of choice for renal colic*. A second dose can be given after 30 minutes if necessary. (*PR diclofenac is an alternative)

Answer 43

Calcium stones • High fluid intake • Low animal protein, low salt diet (a low calcium diet has not been shown to be superior to a normocalcemic diet) • Thiazide diuretics (↑ distal tubular calcium resorption) • Stones < 5 mm will usually pass spontaneously • Lithotripsy, nephrolithotomy may be required

Answer 44

• Cholestyramine ↓ urinary oxalate secretion • Pyridoxine ↓ urinary oxalate secretion

Answer 45

• Allopurinol • Urinary alkalinization e.g. Oral bicarbonate

Answer 46

Stage 1 • Hyperfiltration: ↑ in GFR (60-140 ml/min/1.73m2) • May be reversible Stage 2 (silent or latent phase) • Most patients do not develop microalbuminuria for 10 years • GFR remains elevated Stage 3 (incipient nephropathy) • Microalbuminuria (albumin excretion of 30 - 300 mg/day, dipstick negative) Stage 4 (overt nephropathy) • Persistent proteinuria (albumin excretion > 300 mg/day, dipstick positive) • Hypertension is present in most patients • Histology shows diffuse glomerulosclerosis and focal glomerulosclerosis (kimmelstiel-wilson nodules) Stage 5 • End-stage renal disease, GFR typically < 10ml/min • Renal replacement therapy needed (The timeline given here is for type 1 diabetics. Patients with type 2 diabetes mellitus (T2DM) progress through similar stages but in a different timescale - some T2DM patients may progress quickly to the later stages)

Answer 47

Screening • All patients should be screened annually • Albumin:Creatinine ratio (ACR) in early morning specimen • ACR > 2.5 = microalbuminuria

Answer 48

Management • Dietary protein restriction • Tight glycemic control • BP control: aim for < 130/80 mmHg • Benefits independent of blood pressure control have been demonstrated for ACE inhibitors and angiotensin II receptor blockers - these may be used alone or in combination • Control dyslipidemia e.g. Statins

Answer 49

Collecting an ACR sample • By collecting a 'spot' sample it avoids the need to collect urine over a 24 hour period in order to detect or quantify proteinuria • Should be a first-pass morning urine specimen • If the initial ACR is greater than 30 mg/mmol and less than 70 mg/mmol, confirm by a subsequent early morning sample. If the initial ACR > 70 mg/mmol no need to repeat Interpreting the ACR results • In non-diabetics an ACR > 30 mg/mmol is considered clinically significant proteinuria • In diabetics (ACR > 2.5 in men and ACR > 3.5 in women) is considered clinically significant ACR (mg/mmol)PCR (mg/mmol)Urinary protein excretion (g/24 h) 30 50 0.5 70 100 1

Answer 50

Newly detected microalbuminuria in DM patient → repeat 3-6 months period before starting Rx

Answer 51

ACE-I ARBs

Answer 52

NICE recommend using the albumin:creatinine ratio (ACR) in preference to the protein:creatinine ratio (PCR) when identifying patients with proteinuria as it has greater sensitivity. For quantification and monitoring of proteinuria, PCR can be used as an alternative, although ACR is recommended in diabetics. Urine reagent strips are not recommended unless they express the result as an ACR.

Answer 53

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

Answer 54

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

Answer 55

• Urinary tract infection • Menstruation • Vigorous exercise • Sexual intercourse

Answer 56

• Cancer (bladder, renal, prostate) • Stones • Benign prostatic hyperplasia, Prostatitis. • Urethritis e.g. Chlamydia • Renal causes: IgA nephropathy, thin basement membrane disease

Answer 57

• Urine dipstick is the test of choice for detecting hematuria • Urine microscopy may be used but time to analysis significantly affects the number of red blood cells detected

Answer 58

NICE urgent cancer referral guidelines • Of any age with painless macroscopic hematuria • Aged 40 years and older who present with recurrent or persistent urinary tract infection associated with hematuria • Aged 50 years and older who are found to have unexplained microscopic hematuria

Answer 59

Fanconi syndrome describes a generalised reabsorptive disorder of renal tubular transport in the proximal convoluted tubule resulting in: type 2 (proximal) renal tubular acidosis polyuria aminoaciduria glycosuria phosphaturia osteomalacia

Answer 60

• Cystinosis (most common cause in children) • Sjogren's syndrome • Multiple myeloma • Nephrotic syndrome • Wilson's disease

Answer 61

Renal Tubular Acidosis (RTA) all types of renal tubular acidosis (RTA) are associated with hyperchloremic metabolic acidosis (normal anion gap)

Answer 62

• Inability to generate acid urine (secrete H+) in distal tubule • Hypokalemia • Complications include nephrocalcinosis and renal stones • Causes include idiopathic, RA, SLE, Sjogren's

Answer 63

• ↓ HCO3- reabsorption in proximal tubule • Hypokalemia • Complications include osteomalacia • Causes include idiopathic, as part of Fanconi syndrome, Wilson's disease, cystinosis, outdated tetracyclines • Treat: Bicarb replacement + Thiazide diuretics

Answer 64

Type 4 RTA (hyperkalemic RTA) is not actually a tubular disorder at all nor does it have a clinical picture similar to the other RTAs. It was included in the classification of RTA as it is associated with a mild (normal anion gap) metabolic acidosis due to a physiological ↓ in proximal tubular ammonium excretion. hyperkalaemic

Answer 65

Causes include: • Aldosterone deficiency (hypoaldosteronism): Primary vs. hyporeninemic • Aldosterone resistance: o Drugs: Amiloride, Spironolactone, Trimethoprim, Pentamidine o Pseudohypoaldosteronism • DM

Answer 66

Type 3 RTA (Juvenile RTA) is combined proximal & distal RTA.

Answer 67

Features: • Results from inherited carbonic anhydrase II deficiency. • Mutations in the gene encoding this enzyme give rise to: o Autosomal recessive syndrome of osteopetrosis o Renal tubular acidosis o Cerebral calcification o Mental retardation. • 70% of the reported cases are from the Magreb region of North Africa

Answer 68

Prerenal uraemia - kidneys hold on to sodium to preserve volume

Answer 69

Pre-renal uraemia ('azotemia') ATN 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 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

Answer 70

• Chronic analgesia use • Sickle cell disease • TB • Acute pyelonephritis • Diabetes Mellitus

Answer 71

Features • Fever, loin pain, hematuria • IVU (intravenous urogram or IVP for pyelogram) - papillary necrosis with renal scarring - 'cup & spill'

Answer 72

sterile pyuria Tubulo-interstitial nephritis may cause sterile pyuria but it is not seen with acute glomerulonephritis

Answer 73

Renal Cell Cancer is also known as hypernephroma and accounts for 85% of primary renal neoplasms. It arises from proximal renal tubular epithelium

Answer 74

Associations* • More common in middle-aged men • Smoking • Von hippel-lindau syndrome • Tuberous sclerosis

Answer 75

Diagnosis: • CT scan ± contrast shows contrast enhancing mass

Answer 76

Features • Classical triad: hematuria, loin pain, abdominal mass • Pyrexia of unknown origin • Left varicocele (due to occlusion of left testicular vein) • Endocrine effects: may secrete erythropoietin (polycythemia), parathyroid hormone (hypercalcemia), renin, ACTH • 25% have metastases at presentation

Answer 77

Management • Radical nephrectomy for confined disease • α-interferon and interleukin-2 have been used to ↓ tumor size and also treat patients with metastases • Receptor tyrosine kinase inhibitors (e.g. Sorafenib, sunitinib) have been shown to have superior efficacy compared to interferon-α

Answer 78

Wilm’s Tumor (Nephroblastoma) is one of the most common childhood malignancies. It typically presents in children less than 5 years of age, with a median age of 3 years.

Answer 79

• Abdominal mass (most common presenting feature) • Painless hematuria • Flank pain • Other features: anorexia, fever • Unilateral in 95% of cases • Metastases are found in 20% of patients (most commonly lung)

Answer 80

• Beckwith-Wiedemann syndrome is a inherited condition associated with organomegaly, macroglossia, abdominal wall defects, Wilm's tumor and neonatal hypoglycemia • As part of WAGR syndrome: Wilms Aniridia, Genitourinary malformations, mental Retardation. It results from a deletion on chromosome 11 resulting in the loss of several genes. • Hemihypertrophy • Around one-third of cases are associated with a mutation in the WT1 gene on chromosome 11

Answer 81

most common metastatic/secondary tumor that produce a solitary round shadow in chest cavity is renal in origin

Answer 82

Management • Nephrectomy • Chemotherapy • Radiotherapy if advanced disease • Prognosis: good, 80% cure rate

Answer 83

Renal Vascular Disease is most commonly due to atherosclerosis (> 95% of patients). It is associated with risk factors such as smoking and hypertension that cause atheroma elsewhere in the body. In younger patients however fibromuscular dysplasia (FMD) needs to be considered.

Answer 84

It may present as hypertension, chronic renal failure or 'flash' pulmonary edema.

Answer 85

FMD is more common in young women and characteristically has a 'string of beads' appearance on angiography. Patients respond well to balloon angioplasty. Its response to balloon angioplasty is better than atherosclerosis.

Answer 86

Hypokalemia and metabolic alkalosis may occur due to compensatory hyperaldosteronism.

Answer 87

• MR angiography is now the investigation of choice • CT angiography • Conventional renal angiography is less commonly performed used nowadays, but may still have a role when planning surgery

Answer 88

Renal Artery Stenosis ↓ do MR angiography

Answer 89

Renal involvement in HIV patients may occur as a consequence of treatment or the virus itself. Protease inhibitors such as indinavir can precipitate intratubular crystal obstruction

Answer 90

HIV-associated nephropathy (HIVAN) accounts for up to 10% of end-stage renal failure cases in the United States. Antiretroviral therapy has been shown to alter the course of the disease. There are five key features of HIVAN: • Massive proteinuria • Normal or large kidneys • Focal segmental glomerulosclerosis with focal or global capillary collapse on renal biopsy • Elevated urea and creatinine • Normotension

Answer 91

• Class I: normal kidney • Class II: mesangial glomerulonephritis • Class III: focal (and segmental) proliferative glomerulonephritis • Class IV: diffuse proliferative glomerulonephritis • Class V: diffuse membranous glomerulonephritis • Class VI: sclerosing glomerulonephritis Class IV (diffuse proliferative glomerulonephritis) is the most common and severe form of proliferative GN

Answer 92

• Treat hypertension • Corticosteroids if clinical evidence of disease • Immunosuppressants e.g. Azathioprine/cyclophosphamide

Answer 93

ACE inhibitors are first line and are particularly helpful in proteinuric renal disease (e.g. diabetic nephropathy). As these drugs tend to ↓ filtration pressure a small fall in glomerular filtration pressure (GFR) and rise in creatinine can be expected. Most nephrologists would accept a change of up to 15%. A rise greater than this may indicate underlying renovascular disease. Furosemide is useful as anti-hypertensive in patients with CKD, particularly when the GFR falls to below 45 ml/min*. It has the added benefit of lowering serum potassium. High doses are usually required. If the patient becomes at risk of dehydration (e.g. Gastroenteritis) then consideration should be given to temporarily stopping the drug *the NKF K/DOQI guidelines suggest a lower cut-off of less than 30 ml/min

Answer 94

Goodpasture’s syndrome (AKA anti-glomerular basement membrane disease) Goodpasture's syndrome is rare condition associated with both pulmonary hemorrhage and rapidly progressive glomerulonephritis. Although many diseases can present with these symptoms, the name Goodpasture’s syndrome is usually reserved for the autoimmune disease triggered when the patient’s immune system attacks Goodpasture antigen (a type II hypersensitivity reaction), which is found in the kidney and lung, and in time, causing damage to these organs. It is caused by anti-glomerular basement membrane (anti-GBM) antibodies against type IV collagen.

Answer 95

Goodpasture's syndrome • IgG deposits on renal biopsy • Anti-GBM antibodies

Answer 96

Goodpasture's syndrome is more common in men (sex ratio 2:1) and has a bimodal age distribution (peaks in 20-30 and 60-70 age bracket). Associated with HLA DR2.

Answer 97

Features • Pulmonary hemorrhage • Followed by rapidly progressive glomerulonephritis

Answer 98

Factors which ↑ likelihood of pulmonary hemorrhage • Y oung ♂s • Smoking • Lower respiratory tract infection • Pulmonary edema • Inhalation of hydrocarbons Dehydration may ↓ the likelihood of a pulmonary hemorrhage. Pulmonary edema is associated with ↑ risk

Answer 99

Investigations • Renal biopsy: linear IgG deposits along basement membrane • ↑ transfer factor secondary to pulmonary hemorrhages • Lung biopsy: accumulation of hemosidren laden macrophages with alveoli

Answer 100

Management • Plasma exchange • Steroids • Cyclophosphamide

Answer 101

Hemolytic Uremic Syndrome is generally seen in young children and produces a triad of: • Acute renal failure • Microangiopathic hemolytic anemia • Thrombocytopenia

Answer 102

Causes • Post-dysentery - classically E coli 0157:H7 ('verotoxigenic', 'enterohemorrhagic') • Tumors • Pregnancy • Cyclosporine, the Pill • SLE • HIV Other causes of HUS include S. pneumoniae, Shigella (type 1 and 3), HIV and Coxsackie virus

Answer 103

Investigations • Full blood count: anemia, thrombocytopenia, fragmented blood film • U&E: acute renal failure • Stool culture

Answer 104

• Treatment is supportive e.g. Fluids, blood transfusion and dialysis if required • There is no role for antibiotics, despite the preceding diarrheal illness in many patients • The indications for plasma exchange in HUS are complicated. As a general rule plasma exchange is reserved for severe cases of HUS NOT associated with diarrhea

Answer 105

Phenylketonuria (PKU) is an autosomal recessive condition caused by a disorder of phenylalanine metabolism. This is due to defect in phenylalanine hydroxylase, an enzyme which converts phenylalanine to tyrosine. High levels of phenylalanine lead to problems such as learning difficulties and seizures. The gene for phenylalanine hydroxylase is located on chromosome 12. The incidence of PKU is c. 1 in 10,000 live births

Answer 106

• Usually presents by 6 months e.g. With developmental delay • Child classically has fair hair and blue eyes • Learning difficulties • Seizures, typically infantile spasms • Eczema • 'Musty' odor to urine and sweat

Answer 107

• Guthrie test: the 'heel-prick' test done at 5-9 days of life - also looks for other biochemical disorders such as hypothyroidism • Hyperphenylalaninemia • Phenylpyruvic acid in urine

Answer 108

• Poor evidence base to suggest strict diet prevents learning disabilities • Dietary restrictions are however important during pregnancy as genetically normal fetuses may be affected by high maternal phenylalanine levels

Answer 109

Cystinuria is an autosomal recessive disorder characterized by the formation of recurrent renal stones. It is due to a defect in the membrane transport of cystine, ornithine, lysine, arginine (mnemonic = COLA)

Answer 110

Genetics • Chromosome 2: SLC3A1 gene, chromosome 19: SLC7A9

Answer 111

Features • Recurrent renal stones • Are classically yellow and crystalline, appearing semi-opaque on x-ray

Answer 112

Diagnosis • Cyanide-nitroprusside test

Answer 113

Management • Hydration • D-penicillamine • Urinary alkalinization

Answer 114

Homocystinuria is a rare autosomal recessive disease caused by a deficiency of cystathionine beta synthase. This results in severe elevations in plasma and urine homocysteine concentrations.

Answer 115

Features • Often patients have fine, fair hair • Musculoskeletal: may be similar to Marfan's - arachnodactyly etc • Neurological patients may have learning difficulties, seizures • Ocular: downwards dislocation of lens (Marfan has upward dislocation of lens) • ↑ Risk of arterial and venous thromboembolism except coronaries. • Also malar flush, livedo reticularis

Answer 116

Diagnosis is made by the cyanide-nitroprusside test, which is also positive in cystinuria

Answer 117

Treatment is vitamin B6 supplements

Answer 118

Alkaptonuria: (black urine disease or alcaptonuria) Basics: • Rare inherited genetic disorder of phenylalanine and tyrosine metabolism • Autosomal recessive • Common in Slovakia and the Dominican Republic than in other countries. • Due to a defect in the enzyme homogentisate 1,2-dioxygenase, which participates in the degradation of tyrosine. As a result, a toxic tyrosine byproduct called homogentisic acid (or alkapton) accumulates in the blood and is excreted in urine in large amounts. Excessive homogentisic acid causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves as well as precipitating as kidney stones.

Answer 119

Alkaptonuria is often asymptomatic, but the sclera may be pigmented (often only at a later age), and the skin may be darkened in sun-exposed areas and around sweat glands; sweat may be colored brown or black. Kidney stones and stone formation in the prostate (in men) are common and may occur in more than a quarter of cases. The main symptoms of alkaptonuria are due to the accumulation of homogentisic acid in tissues. In the joints this leads to cartilage damage, specifically in the spine, leading to low back pain at a young age in most cases. Cartilage damage may also occur in the hip and shoulder. Joint replacement surgery (hip and shoulder) is often necessary at a relatively young age. Valvular heart disease, mainly calcification and regurgitation of the aortic and mitral valves, may occur, and in severe and progressive cases valve replacement may be necessary. Coronary artery disease may be accelerated in alkaptonuria. A distinctive characteristic of alkaptonuria is that ear wax exposed to air turns red or black (depending on diet) after several hours because of the accumulation of homogentisic acid

Answer 120

Treatment with nitisinone, which suppresses homogentisic acid production, is being studied

Answer 121

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

Answer 122

BPH typically presents with lower urinary tract symptoms (LUTS), which may be categorized into: • Voiding symptoms (obstructive): weak or intermittent urinary flow, straining, hesitancy, terminal dribbling and incomplete emptying • Storage symptoms (irritative) urgency, frequency, urgency incontinence and nocturia • Post-micturition: dribbling • Complications: urinary tract infection, retention, obstructive uropathy

Answer 123

Management options • W atchful waiting • Medication: α-1 antagonists, 5 α-reductase inhibitors. The use of combination therapy was supported by the medical therapy of prostatic symptoms (MTOPS) trial • Surgery: transurethral resection of prostate (TURP)

Answer 124

α-1 antagonists e.g. tamsulosin, alfuzosin • ↓ smooth muscle tone (prostate and bladder) • Considered first-line, improve symptoms in around 70% of men • Adverse effects: dizziness, postural hypotension, dry mouth, depression

Answer 125

5 α-reductase inhibitors e.g. finasteride • Block the conversion of testosterone to dihydrotestosterone (DHT), which induces BPH • Unlike α-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. They may also ↓ PSA concentrations by up to 50% • Adverse effects: erectile dysfunction, ↓ libido, ejaculation problems, gynecomastia

Answer 126

Risk Factors: • Age • ↑ fat diet • Family Hx • BPH is not a risk factor

Answer 127

Localized disease = T1/2 T1 - clinically unapparent disease: • If life expectancy < 10 years then watchful waiting • If life expectancy > 10 years then offer: o Radical prostatectomy o Radical radiotherapy T2 - palpable disease confined to prostate • Radical prostatectomy • Radical radiotherapy (often if older patient)

Answer 128

Locally advanced disease (T3/4) • T3 = beyond prostatic capsule • T4 = involves bladder neck or rectum • Most men will have occult mets Radiotherapy

Answer 129

Disseminated disease - hormonal therapy • Synthetic GnRH agonist o E.g. Goserelin (zoladex) is a synthetic GnRH agonist which provides negative feedback to the anterior pituitary. o Cover initially with anti-androgen to prevent rise in testosterone • Anti-androgen: o Cyproterone acetate prevents DHT binding from intracytoplasmic protein complexes • Orchidectomy

Answer 130

Bladder cancer: is a common urological cancer with most cases being transitional cell carcinomas. It has a ♂:♀=3:1 with women generally having a worse prognosis than men. The most classical presentation is with total, gross, painless hematuria.

Answer 131

• Smoking • Occupational: aniline dyes used in printing and textile industry, rubber manufacture • Aromatic amines • Prior radiation treatment to the pelvis • Exposure to a urinary metabolite of cyclophosphamide (acrolein). • Schistosomiasis (S. hematobium infection)

Answer 132

• Mutations on 17p13.1, the gene coding for p53, mutations of which are associated with high- grade bladder cancer • Mutation on 9p15 and 9p16, another tumor suppressor gene associated with low grade and superficial tumors.

Answer 133

• Drugs: cyclophosphamide

Answer 134

An inherited disorder of type IV collagen that causes thinning of the basement membrane. It may affect up to 5% of the population and about 30% patients report a family history of haematuria. Diagnosis is usually based on the history of persistent haematuria, normal kidney function and family history of haematuria without kidney failure. It is generally a benign disorder and biopsy is rarely indicated.

Answer 135

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.

Answer 136

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.

Answer 137

Treatment of calciphylaxis focuses on reducing calcium and phosphate levels, controlling hyperparathyroidism and avoiding contributing drugs such as warfarin and calcium containing compounds.

Answer 138

Acute interstitial nephritis (AIN) typically arises following drug therapy in the majority of cases (~75%), with infections and systemic vasculitides forming the rest. drugs: the most common cause, particularly antibiotics penicillin rifampicin NSAIDs allopurinol furosemide systemic disease: SLE, sarcoidosis, and Sjögren's syndrome infection: Hanta virus , staphylococci

Answer 139

Definitive diagnosis is done by renal biopsy, which is typically reserved for when the diagnosis is unclear or if another aetiology is suspected to occur concurrently/in equal likelihood. Investigations sterile pyuria white cell casts

Answer 140

Features fever, rash, arthralgia eosinophilia mild renal impairment hypertension

Answer 141

Pathophysiology histology: marked interstitial oedema and interstitial infiltrate in the connective tissue between renal tubules

Answer 142

Overview amyloidosis is a term which describes the extracellular deposition of an insoluble fibrillar protein termed amyloid amyloid is derived from many different precursor proteins in addition to the fibrillar component, amyloid also contains a non-fibrillary protein called amyloid-P component, derived from the acute phase protein serum amyloid P other non-fibrillary components include apolipoprotein E and heparan sulphate proteoglycans the accumulation of amyloid fibrils leads to tissue/organ dysfunction

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Classification systemic or localized further characterised by precursor protein (e.g. AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments)

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Diagnosis Congo red staining: apple-green birefringence serum amyloid precursor (SAP) scan biopsy of rectal tissue

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-the most common form of amyloidosis -L for immunoglobulin Light chain fragment -due to myeloma, Waldenstrom's, MGUS -features include: nephrotic syndrome, cardiac and neurological involvement, macroglossia, periorbital eccymoses

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-A for precursor serum amyloid A protein, an acute phase reactant -seen in chronic infection/inflammation e.g. TB, bronchiectasis, rheumatoid arthritis -features: renal involvement most common feature

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Beta-2 microglobulin amyloidosis -precursor protein is beta-2 microglobulin, part of the major histocompatibility complex -associated with patients on renal dialysis

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Diagnosis: • Primary tumour can be very small and go undetected on testicular examination. • Marked ↑ in β-HCG in the presence of a normal AFP and CEA. • Scrotal ultrasound is used to support the diagnosis • CTs are of significant value for staging.

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Management: • Choriocarcinoma is extremely sensitive to cisplatin based chemotherapy, with cure rates of up to 80% being achievable, even in advanced disease.