Renal Flashcards
Nephrotic syndrome is associated with:
A. Elevated serum albumin
B. Reduced LDL cholesterol
C. Normal glomerular filtration barrier
D. Decreased hepatic synthesis of coagulation factors
E. Increased susceptibility to infection, particularly gram-positive bacteria
Answer: E - increased susceptibility to infection
Nephrotic syndrome is associated with hypoalbuminuria and peripheral oedema.
Hepatic cholesterol and lipoprotein synthesis are increased due to ramped up protein synthesis as compensation for low albumin
Hypercoagulability results from increase hepatic synthesis of coagulation factors (e.g. fibrinogen) and loss of regulatory factors (anti-thrombin III, protein C/S) in urine. Renal vein thrombosis can complicate all forms of nephrotic syndrome, especially membranous nephropathy.
Loss of IgG and complement is thought to reduce cell mediated immunity and predispose to Gram positive infections in particular.
Glomerular diseases include a wide range of immune and non-immune insults that may target and injure the podocyte. Which of these is true?
A. The degree of podocytopenia predicts progression of diabetic kidney disease
B. Podocyte proliferation is a feature of minimal change disease
C. Foot process effacement is seen in membranous nephropathy
D. Expression of slit diaphragm proteins are not altered in nephrotic disorders
E. Podocytes do not undergo programmed cell death
Answer: A - The degree of podocytopenia predicts progression of diabetic kidney disease
Podocyte proliferation is a feature of collapsing glomerulopathy. Foot process effacement is seen in minimal change disease. Podocytes respond to immune complex-mediated injury by producing inflammatory mediators and oxidative injury is a prominent feature in membranous nephropathy. Podocytes can undergo programmed cell death/apoptosis and when lost they are not replaced by adjacent viable podocytes which resulting leaking of the GF barrier.
About 30-40% of adult patients with idiopathic membranous nephropathy develop progressive disease. Which of the following is a risk factor for progression?
A. Normal kidney function at presentation
B. Normal BP
C. Age <50years
D. Kidney biopsy showing glomerulosclerosis and tubulointerstitial fibrosis
E. Female sex
Answer: D - Kidney biopsy showing glomerulosclerosis and tubulointerstitial fibrosis
Prognostic risk factors for progression of idiopathic membranous nephropathy include:
- Proteinuria
- Impaired renal function at presentation
- Hypertension
- Males aged >50yrs
- Non-Asians
- Biopsy changes of sclerosis/fibrosis etc
A high proportion of patient with idiopathic MN have circulating antibodies to M-type phospholipase A2 receptor (PLA2R), a podocyte transmembrane protein.
PLA2R in 70-80% idiopathic MN.
- If persisting or rising then unlikely to spontaneously remit
- Responds to treatment more quickly than proteinuria
Which one of the following pathophysiological processes is observed in vascular calcification in chronic kidney disease?
A. Vascular smooth muscle cell apoptosis driven by hypophosphataemia
B. Osteochondrogenic metaplasia driven by hypophosphataemia
C. Elevated Klotho expression
D. Impaired soft tissue calcification defences
E. Elevation in serum fetuin levels
Answer: D - Impaired soft tissue calcification defences
Vascular calcification in CKD involves major disturbance of calcium/phosphate homeostasis (and low fetuin levels)
Vascular smooth muscle cell apoptosis and osteochondrogenic metaplasia are drive by HYPERphosphataemia, worsened by iatrogenic hypoparathyroidism and low-turnover bone disease.
Klotho is a protein expressed in kidney tubules and parathyroid cells, mediating the role of FGF-23 (fibroblast growth factor 23) in bone-kidney-parathyroid control of phosphate and calcium. Mice with knockout genes for Klotho (i.e. nil Klotho expression) demonstrate premature aging and CKD-BMD mediated by hyperphosphataemia. CKD can be seen as a state of hyperphosphataemia-induced accelerated aging and KLOTHO DEFICIENCY.
Klotho deficiency is seen very early in CKD (even stage 1) and continues to decline as CKD progresses, causing FGF-23 resistance with large FGF-23 and PTH increases.
EMQ
A. Proximal renal tubule B. Thin descending limb of loop of Henle C. Thin ascending limb of Henle's loop D. Thick ascending limb of loop of Henle E. Distal convoluted tubule F. Cortical collecting duct G. Medullary collecting duct H. Papillary duct
- Aldosterone stimulates which part of the renal tubule to reabsorb sodium?
- Atrial natriuretic peptide affects which part of the renal tubule to inhibit sodium reabsorption?
- Which part of the tubule is the site for excretion of trimethoprim?
- Dapagliflozin exerts its effect on which part of the renal tubule?
- Where is phosphate mainly reabsorbed after being filtered by the glomerulus?
- Answer: F - Aldosterone stimulates Na reabsorption in the cortical collecting duct.
- Answer: G - ANP stimulates inner medullary collecting ducts to inhibit Na reabsorption. The main stimulus is atrial distension (as in volume expansion/overload)
- Answer: A - Trimethoprim is actively excreted in the Proximal tubule. Creatinine is secreted actively by the same process so Trimethoprim can inhibit this and elevate serum creatinine.
- Answer: A - Dapaglifozin inhibits sodium glucose transports 2 (SGLT2) which is in the proximal tubule and accounts for 90% of glucose reabsorption.
- Answer: A - Phosphate is reabsorbed in the proximal tubule. When serum PO4 increases (eight high intake or reduced GFR) the amount reabsorbed decreases to the physiologically needed level. FGF-23 inhibits the reabsorption as down elevated PTH.
Define nephrotic syndrome
List the causes of nephrotic syndrome
Nephrotic syndrome =
- Nephrotic range proteinuria
- >3.5g/24 hours
- Microalbuminauria = 30-300mg/day (i.e. 3.4-34mg/mmol of spot ACR)
- Macroalbuminuria > 300mg/day (i.e. >34mg/mmol of spot ACR) - Hypoalbuminaemia
- Peripheral oedema
Causes of nephrotic syndrome
- Primary glomerular disease:
1. Minimal change disease
2. FSGS
3. Membranous nephropathy
4. Membranoproliferative GN (either nephrotic or nephritic) - Secondary glomerular disease:
1. Diabetic nephropathy
2. Amyloid nephropathy (AL light chain i.e. myeloma/plasma cell disorder), (AA i.e. chronic inflammation e.g. RA)
3. Lupus nephritis
A 60 year old man with end stage diabetic nephropathy received his first kidney transplant 6 months ago. Post transplantation, he had one episode of severe vascular rejection which was treated with anti-thymoglobulin (ATG). His graft function stabilised with serum creatinine 190 while taking tacrolimus, MMF and prednisolone. However his renal function has progressively worsened in the past 2 weeks. His preliminary kidney biopsy result reveals significant tubulitis, interstitial lymphocyte infiltration and intranuclear inclusion bodies.
Which one of the following is NOT a treatment option?
A. Intravenous cidofovir to eradicate BK virus B. IV methylprednisolone C. Oral ciprofloxacin D. Switch MMF to Leflunomide E. Reduce tacrolimus and MMF doses
Answer: B - IV methylprednisolone
The cause of renal deterioration in this case is BK virus nephropathy. BK nephropathy is associated with:
- Aggressive immunosuppression during acute rejection i.e. ATG
- Older age, females
- HLA Dr mismatching
Management is difficult but reduction of immunosuppression is the cornerstone.
Cidofovir can inhibit viral DNA synthesis (benefit in case series) - limited by substantial nephrotoxicity
Leflunomide is both immunsuppressive and has anti-viral properties (single centre reports of beneft, no RCTs)
Ciprofloxacin has been shown to have some benefit.
A 72year old man presents with severe abdominal pain in the last 6 hours. The past medical history is significant for congestive heart failure, hypertension and type 2 diabetes on insulin, stage 4 CKD with baseline creatinine of 180). His medications include insulin, perindopril, atenolol, pravastatin, aspirin. He has been seen by the surgical registrar who suspects the patient is suffering from an ischaemic bowel and requires urgent abdominal CT with IV contrast. The radiology registrar is concerned about renal failure and consults you about contrast-induced nephropathy. Which of the following recommendations would you make?
A. Give IV Normal saline first and delay CT 12 hours
B. Give oral NAC 600mg BD for 2 days because of concern regarding IHD
C. Start IV normal saline, proceed with contrast then start haemodialysis after the CT
D. Stop perindopril, give IV saline and use furosemide to force diuresis
E. Give IV sodium bicarbonate 1 hour before contrast and 3 hours after CT
Answer: E - Give IV sodium bicarbonate 1 hour before contrast and 3 hours after CT
Contrast induced AKI:
- Hydration with normal saline is well establish when given 12 hours before and 12 hours after (not in this case given urgent need for scan)
- Alkalinisation may protect against free radical injury and studies have noted either equivalent or better outcomes with bicarb vs normal saline.
- NAC has not been shown consistently to have benefit whether oral or IV
A 62 year old man has stage 4 CKD due to diabetic nephropathy and is found to have anaemia secondary to CKD. His EPO dose was recently reduce due to Hb 140g/L. However he complains his golf performance has deteriorated at the current dose and Hb of 110g/L. He would like to increase the EPo dose and keep his Hb at 140g/L. Which one of the following has been observed with Hb target >130g/L
A. Increased risk of stroke B. Reduced risk of stroke C. Increased rate of renal function deterioration D. Improved BP control E. Decrease in frequency of headache
Answer: A - Increased risk of stroke
Hb >130g/L increases risk of stroke, headaches, hypertension, VTE
A 56 year old man with advanced CKD presents with proximal muscle weakness. The serum potassium is 6.8mmoL. Which one of the following treatment would lower his serum potassium most quickly?
A. 10mL 10% calcium gluconate IV B. 100mL of 8.4% sodium bicarb IV C. 50mL of 50% glucose and 10 units of short-acting insulin D. 30g resonium orally E. 30g resonium per rectum
Answer: C - 50mL of 50% glucose and 10 units of short-acting insulin subcut
Sodium bicarbonate is effective if severe metabolic acidosis but will take 2 hours for effect.
A 74 year old man is being managed at the haematology clinic for suspected myeloma. Over the past few weeks he has had increasing dyspnoea, lethargy, reduced exercise tolerance and increased lower limb oedema.
On examination he appears pale, BP is 98/68, HR 89bpm. Heart sounds are normal but there are bilateral crackles in his chest with pitting lower limb oedema. Blood results are below. The 24 hour urine protein is 9g/day. Which of the following is the most likely cause of his proteinuria?
Hb 102 WCC 8.7 Platelets 185 Na 140 K 4.3 Creatinine 135 Albumin 15
A. AA amyloidosis B. AL amyloidosis C. BPP (B-protein precursor) amyloidosis D. Cystatin C amyloidosis E. Mesangiocapillary glomerulonephritis
Answer: B - AL amyloidosis
AL amyloidosis is associated with light chain deposition and is caused by multiple myeloma. He has likely both cardiac and renal amyloid given the clinical picture of heart failure with nephrotic syndrome.
In developed countries, which of the following bone disorders is most frequent in patients receiving maintenance haemodialysis?
A. Osteitis fibrosa cystica B. Adynamic bone disease C. Osteomalacia D. Dialysis related amyloidosis E. Aluminium bone disease
Answer: B - Adynamic bone disease
Adynamic bone disease amongst haemodialysis patients has been increasingly common due to suppression of PTH with calcium and potent vitamin D analogues.
Dialysis related amyloidosis is causes by beta-2-microglobulin deposition as amyloid deposits. It is relatively common in those on dialysis for more than 5 years. Newer dialysis membranes have a more effective clearance. It usually presents as carpal tunnel and shoulder pain.
A 28 year old woman presents with nausea and vomiting and is found to have a platelet count of 60, Hb of 87 and creatinine of 285. Which one of the following is consistent with a diagnosis of atypical haemolytic uraemic syndrome?
A. Markedly suppressed ADAMTS13 activity in blood
B. Stool culture positive for Shiga producing E. Coli
C. A mutation in the gene encoding factor H
D. A mutation in the gene encoding ADAMTS13
E. A normal haptoglobinq
Answer: C - A mutation in the gene encoding factor H
aHUS is characterised by MAHA with fall in platelet count, haemolytic anaemia and renal impairment.
It results for terminal complement dysregulation and is associated with deficiencies in various proteins (factor H, factor I, thrombomodulin, membrane cofactor protein).
Plasmapheresis is an effective treatment and there is an increasing role for terminal complement inhibitor (anti-C5 antibody Eculizumab).
TTP is a related disorder resulted from ADAMTS13 deficiency (protease which cleaves von willebrand factor multimers)
Which one of the following is NOT a risk factor for contrast induced acute kidney injury?
A. Congestive heart failure B. Metformin C. Multiple myeloma D. NSAIDs E. Sepsis
Answer: B - Metformin
Non modifiable risk factors: Older age CKD Diabetes mellitus CCF Renal transplant Multiple myeloma
Modifiable risk factors:
- Hypotension, anaemia
- Dehydration
- Low serum albumin
- ACEi/ARBs
- Diuretics
- NSAIDs
- Volume of conrast
Metformin is not nephrotoxic. The rationale is that if an AKI develops then this will impair metformin metabolism and lead to lactic acidosis.
Which one of the following anti-hypertensive drugs should not be used in patients with pre-eclampsia?
A. Nifedipine B. Methyldopa C. Irbesartan D. Labetalol E. Hydralazine
Answer: C - Irbesartan
ARBs teratogenic
