SCE Questions Dr T Scale @drscale86 http://www.welshkidney.org/

#RenalSCE

Question 1 A 33 year old man presented with a renal calculi, he eventually passes a stone which gets analysed and is mostly calcium oxalate in its composition. He is wondering what are the chances of him getting another stone. What is the chance of him having one or more stones in the next 10 years? 1. 20% 2. 30% 3. 50% 4. 60% 5. 80%

Question 2 A 24 year old man presents with his third renal stone. Microscopy reveals the image shown below. Following his previous stones he has been drinking 4-5 litres of water per day, he is on a low salt diet and is taking potassium citrate. What is the most appropriate medication to start?

1. Tiopronin 2. Sodium Bicarbonate 3. Bendroflumethiazide 4. Amiloride

5. Perindopril Taken from Wikipedia Lance Wheeler Cystinuria

• AR Inheritance • Prevalence 1:7000 • 1-2% all stone formers • Cystinuria is the most common defect in the transport of an amino acid. • Often confused with Cystinosis (doesn’t cause cysteine stones) • Cystine is not the only amino acid which is poorly reabsorbed in cystinuria but it is the least soluble of all naturally occurring amino acids. • Cystine precipitate out of urine forming calculi in the urinary tract. Cystinuria treatment

• Hydration • Low sodium diet (sodium promotes cysteine accumulation in urine) • Urine alkalisation –  Potassium Citrate, if not tolerated – Sodium bicarbonate (sodium content – other stones)  Changing diet – more fruit and veg less meat • Chelation  Tiopronin  Penicillamine  Captopril http://rarerenal.org/patient-information/cystinuria-patient-information/ http://uroweb.org/guideline/urolithiasis Question 3 A 55 year man presents with his 5th renal stone in the last 2 years. His past medical history includes diabetes, hypertension and morbid obesity(Roux-en-Y) treated with an operation 5 years previously. His BMI is now 28. His eGFR is now down to 25mls/min. What is the most likely reason for his renal stone?

1. Fat Malabsorption 2. Increased green smoothie intake 3. High sodium intake 4. Excess glycoxylate production due to enzyme deficit 5. Autosomal Recessive mutation of SLC3A1 gene Enteric Hyperoxaluria

• The result of malabsorption – from gastric bypass surgeries (Roux-en-Y) or other causes of malabsorption such as - orlistat, pancreatitis, etc. • Fat malabsorption leads to increased oxalate absorption.

• Other causes of oxalate nephropathy  High doses of intravenous doses of vitamin C,  Ethylene glycol - monohydrated calcium oxalate crystals may be seen with ethylene glycol toxicity.

• Some foods/drinks containing large amounts of oxalate  Star fruit,  Green smoothie  Rhubarb Treatment

• Calcium carbonate  Pre meals

• Reversal of surgery http://dramitgarg.com/diabetic-metabolic-surgery/laparoscopic-roux-en-y-gastric-bypass-metabolic/ Weddelites: Calcium oxalates 2(H2O)

Dihydrate

Whewellites: calcium oxalates (H2O)

Monohydrate

• Calcium oxalate crystals can be found in urine pH values ranging from <5.5 to 6.7 but are seen mostly with • pH < 5.8.

http://urine.optmq.connexence.com/home/home_eng_v2.html Other stones http://urine.optmq.connexence.com/home/home_eng_v2.html

Brushite

CaH2PO4(2H2O) (Like alkaline urine)

Struvite

NH4MgPO4·6H2O (Like alkaline urine)

Urate

C5H4N4O3 (Like acidic urine) More on stones

Click here Question 4 51 Man, originally presented in childhood with failure to thrive, hypophospataemia, episodic hypovalaemia, glycosuria, aminoaciduria hyperchloraemic metabolic acidosis and nephrocalcinosis (as shown below). Developed progressive renal impairment. What is this most likely cause of this condition.

1. Cystinosis 2. Lowe oculo-cerebral-renal syndrome 3. Gordons syndrome 4. Dent Disease 5. Lead Poisoning https://radiopaedia.org/cases/ Causes of Fanconi Syndrome

Genetic Drugs Cisplatinum • Dent Disease (X-linked recessive Tenofovir nephrolithiasis) Ifosfamide (NT) • Cystinosis Gentamicin Nivolumab • Tyrosinaemia type 1 • Galactosaemia Heavy metals Lead • Wilson’s disease Cadmium • Lowe oculo-cerebral-renal syndrome Mercury (NA) • Mitochondrial myopathies M-protein disorders Amyloidosis Light chain disease Dent Disease • X-linked recessive – mainly affects males

• While symptoms and severity vary, they usually begin in childhood and worsen over time.

• The most common feature of Dent disease is proteinuria (protein in the urine). Other common features; hypercalciuria, nephrocalcinosis and renal calculi.

• Less common features include rickets and mildy short stature.

• Progressive kidney problems often lead to end stage renal failure by early to mid-adulthood.

• There are two forms of Dent disease which are distinguished based on their genetic causes.  Dent disease type 1 is caused by a mutation in the CLCN5 gene.  Dent disease type 2 is caused by a mutation in the OCRL gene. Males with this form are also at increased risk for mild intellectual disability and hypotonia.

https://rarediseases.info.nih.gov/diseases/13105/de nt-disease https://www.researchgate.net/publication/304992444_Rare_case_of_nephrocalcinosis_in_a_14-year- old_girl_Answers Familial

Primary

https://encrypted- https://www.science tbn0.gstatic.com/images?q=tbn:ANd9GcSwa9ynwCyQK4CCqgo0cYIXEuqgVbGn3xC6 emkHSSeCh3GdhBlgOA direct.com Question 5 33 year old man, originally presented at 6 months of age with failure to thrive, renal impairment and photophobia. In childhood he had glycosuria and aminoaciduria. It is documented that he has hepatomegaly He developed renal failure requiring dialysis at the age of 10. He has received a renal transplant and is treated with mercaptamine. He sees you in transplant clinic looking to discuss planning a family. He wishes to know the inheritance of this condition?

1. Autosomal Recessive 2. Autosomal Dominant 3. X – linked Recessive 4. X – linked Dominant 5. Spontaneous Mutation Cystinosis

• Autosomal Recessive defect in the transport of cystine out of lysosomes

• Fanconi syndrome

• Photophobia (corneal cystine crystals)

• Hypothyroidism

• Renal failure - ~10 years of age

• Diabetes from pancreatic involvement

• Hepatomegaly Treatment: Cysteamine (mercaptamine) • Infertility • Epilepsy & cerebral atrophy Monitor levels of leukocyte cystine levels

Stones Those at risk of recurrent stones General factors Early onset of urolithiasis (especially children and teenagers) Familial stone formation Brushite-containing stones (CaHPO4.2H2O) Uric acid and urate-containing stones Infection stones Solitary kidney (the kidney itself does not particularly increase the risk of stone formation, but prevention of stone recurrence is of more importance) Diseases associated with stone formation Hyperparathyroidism Metabolic syndrome Nephrocalcinosis Polycystic kidney disease (PKD) Gastrointestinal diseases (i.e., jejuno-ileal bypass, intestinal resection, Crohn’s disease, malabsorptive conditions, enteric hyperoxaluria after urinary diversion) and bariatric surgery [19] Sarcoidosis Spinal cord injury, neurogenic bladder Environmental factors Chronic lead exposure Genetically determined stone formation Cystinuria (type A, B and AB) Primary hyperoxaluria (PH) Renal tubular acidosis (RTA) type I 2,8-Dihydroxyadeninuria Xanthinuria Lesch-Nyhan syndrome Cystic fibrosis Drug-induced stone formation (see Table 4.11) Anatomical abnormalities associated with stone formation Medullary sponge kidney (tubular ectasia) Ureteropelvic junction (UPJ) obstruction Calyceal diverticulum, calyceal cyst Ureteral stricture Vesico-uretero-renal reflux Horseshoe kidney Ureterocele

Strength Recommendations Rating Prescribe thiazide + potassium citrate in case of hypercalcuria. Strong 1a Advise oxalate restriction if hyperoxaluria is present. Weak 2b Offer potassium citrate in enteric hyperoxaluria. Weak 3-4 Offer calcium supplement in enteric hyperoxaluria. Weak 2 Advise reduced dietary fat and oxalate in enteric hyperoxaluria. Weak 3 Prescribe potassium citrate and sodium bicarbonate in case of Strong 1b hypocitraturia. Prescribe allopurinol in case of hyperuricosuria. Strong 1a Offer febuxostat as second-line treatment of hypericosuria. Strong 1b Advise avoiding excessive intake of animal protein in Strong 1b hypericosuria. Advise restricted intake of salt if there is high urinary sodium Strong 1b excretion. Autosomal Primary hyperoxaluria type 1 is caused by mutations in a gene called AGXT. This Recessive gene gives the body instructions for making an enzyme called alanine-glyoxylate aminotransferase. This enzyme is found in cell structures called peroxisomes in liver cells. It converts a compound called glyoxylate to the amino acid glycine.

Mutations in the AGXT gene lead to a decrease in the amount or function of the enzyme, preventing the breakdown of glyoxylate. This is turn causes glyoxylate to accumulate, and it is converted to oxalate instead of glycine. Excess oxalate that is not excreted from the body then combines with calcium to form calcium oxalate, which damages the kidneys and other organs. https://rarediseases.info.nih.gov/diseases/2835/primary-hyperoxaluria-type-1

Recommendation Strength rating Prescribe pyridoxine for primary hyperoxaluria. Strong

Liver and Kidney transplant https://www.youtube.com/watch?v=rBSkVgFABFo Radiopaque Poor Radiolucent radiopacity Calcium oxalate Magnesium dehydrate Uric acid ammonium phosphate (Wheddellite) Calcium oxalate monohydrate Ammonium urate (Whewellite) Cystine Calcium phosphates Xanthine

Brushite Drug-stones Crystalopathies/stones

Co-Trimoxazole

Aciclovir

Ciprofloxacin

Indinavir / other proteasome inhibitors Recommendations Strength rating

Prescribe thiazide in case of Strong hypercalciuria. Advise patients to acidify their Weak urine in case of high urine pH. Recommendation Strength rating Prescribe pyridoxine for primary hyperoxaluria. Strong

Recommendations Strength rating Prescribe potassium citrate. Weak Advise patients to take calcium supplements with meals. Strong Advise patients to follow a diet with a low fat and oxalate content. Weak

Recommendations Strength rating Prescribe potassim citrate to alkalinise the urine in urate stone Strong formers. Prescribe allopurinol in hyperuricosuric urate stone formers. Strong

Recommendations Strength rating Surgically remove the stone material as completely as possible. Strong Prescribe antibiotics in case of persistent bacteriuria. Strong Prescribe ammonium chloride, 1 g, two or three times daily to Weak ensure urinary acidification. Prescribe methionine, 200-500 mg, one to three times daily, as an Weak alternative, to ensure urinary acidification. Renal Tubular Acidosis RTA 2 – Proximal RTA 1 – Distal Hypokalaemia worsens with increase in pH Hypokalaemia improves with increase in pH • Fanconi • Connective tissue - Sjogrens, SLE/RA • Lowe (XL) • Drugs – Amphotercin, Toluene, • Dent (XL) ifosfamide, lithium • Cystinosis (AR) • Sickle cell • Metals – Wilsons, Lead, Cadmium • Immunoglobulins - Cryoglobulins, • Drugs – Tenofovir, Cisplatin, dysparaprotein – MM,AL,LCDD Gentamicin, Tetracyclines, • Interstitial nephritis Acetazolamide, Topiramate, • Transplant rejection lenalidomide, ifosfamide • Hypercalcaemia • Hereditary fructose deficiency • Nephrocalconosis • Myeloma/LCDD • Hereditary • Sjogrens RTA 4 with RTA 1 with hyperkalaemia hyperkalaemia • Diabetes Mellitus • Lupus • Sickle cell • Obstruction • Lead • Sickle cell • Lupus • Pseudohypoaldosteronism type I/II • Heparin • Amiloride • Calcineurin inhibitor • Pentamidine • Obstruction Other tubular Disorders

Acidosis Gordon BP syndrome

Hypomagnesaemi RTA Type 1&2 RTA Type 4 a & Hypercalcuria Potassium

PHA type 1 Liddle Alkalosis Syndrome Conn Syndrome BP Glucocorticoid Remedial aldosteronism

Potassium

Gitelman Bartter Proximal Convoluted Tubule Disturbance of active transport process pRTA Fanconi syndrome Dent syndrome Lowe syndrome Loop of Henle Bartter (NKCC2) Familial hypomagnesaemia with hypercalciuria (Claudin 16 or 19) Distal Convoluted Tubule Gitelman Gordon (NCC) Distal RTA Collecting duct Liddle Pseudohypoaldosteronism (ENAC) Nephrogenic D I (AVRP2 or AQP2) Hereditary SIADH (AVP-NP2) Distal RTA (vH+ATPase, AE1) http://www.clinsci.org/content/118/1/1