Renal Flashcards
What is nephrotic syndrome characterised by? (hint Protein LEAC)
Heavy proteinuria >3.5 g/d, hypoalbumniaemia, oedema and hyperlipidaemia. Protein Lipids Edema Albumin low Cholesterol up
What dietary modification is of most benefit in nephrotic syndrome?
Low Na diet
IgA nephropathy. Cause? Epid? Clin? RF? Dx? Tx?
IgA nephropathy may primarily involve only one kidney or may be secondarily associated with other conditions such as HIV infection, chronic liver disease, IBD or coeliac disease.
Patho
IgA nephropathy, the most common primary glomerulonephritis, is an immune complex disease in which IgA antigen-antibody complexes are deposited primarily in the mesangium.
IgA nephropathy may primarily involve only the kidney or may be secondarily associated with other conditions such as HIV infection, chronic liver disease, inflammatory bowel disease, or celiac disease. IgA nephropathy is the renal lesion of Henoch-Schönlein purpura, a systemic vasculitis most commonly seen during childhood.
Epid:
Primary IgA nephropathy occurs at any age and has a predilection to develop in men who are white or Asian. Approximately 20% to 30% of patients have progressive disease that can lead to ESKD within 10 to 20 years of onset.
RF:
Risk factors associated with progressive CKD include younger age at onset; hypertension; proteinuria ≥1 g/24 h; elevated serum creatinine levels; low GFR; and secondary glomerulosclerosis, chronic tubulointerstitial changes, and crescents on biopsy. Persistent proteinuria (≥1 g/24 h) and hypertension are two modifiable risk factors that increase the risk of progression to advanced CKD.
Clinical:
Most patients with IgA nephropathy are asymptomatic at presentation, with only microscopic hematuria and proteinuria discovered on evaluation of the urine.
A common presentation of primary IgA nephropathy is recurrent gross hematuria occurring synchronously with an episode of respiratory (“synpharyngitic hematuria”) or gastrointestinal infection.
This may be associated with acute kidney injury precipitated by occlusion of tubular lumina by erythrocytes and erythrocyte casts.
Less frequently, patients may present with the nephrotic syndrome or RPGN.
Dx:
Diagnosis is confirmed by kidney biopsy, which demonstrates mesangioproliferative glomerulonephritis with IgA-dominant mesangial immune deposits on immunofluorescence microscopy.
Mx:
Corticosteroids with immunosuppressive agents and antiplatelet agents may be beneficial in the management of primary MPGN but more than 50% of patients progress to advanced CKD.
Treatment of secondary MPGN I is directed toward the underlying cause.
What is the most common extra-renal manifestation of PCOS?
Hepatic cysts - 94% Mitral valve prolapse 25% Abdominal hernia 10% Intracranial aneurysm 8% Colonic diverticuli
Which drug commonly causes AIN?
Antibiotics (Betalactams - pen, cephal, carbo, fluoroquinolones - cipro, norflox, moxiflox, sulfonamides - trimetho) and PPI e.g. ciproflox)
Patient with LVEF 16% and oliguric renal failure with symptoms. What intervention is appropriate?
Insertion of tenckhoff catheter for peritoneal dialysis, minimise risk of acute ischaemia.
Haemodialysis not suitable due to cardiac failure.
Which organism is most likely in a pt on peritoneal dialysis with abdo infection?
S. epidermis 50%
Culture negative infections 20%
Gram -ve 15%
T/F. Proteinuria is the strongest predictor of poor outcome in a patient with chronic kidney disease?
True, increases risk by 4-fold
Which antigen is targeted in Idiopathic membranous nephropathy?
Phospholipase A2 receptor (NEJM)
MOA Sirolimus? Indications?
mTOR inhibitor. Prevents action of B cells and T cells by inhibiting IL-2
Indication: post transplant anti-rejection, Coronary stents
AE: impaired wound healing, myelosuppresion, pneumonitis, infertility
Which circulating factor causes FSGS (Focal segmental glomerulosclerosis)?
suPAR (Nature, 2011)
In post-kindey tranplant, switching to sirolimus will reduce risk of death. T/F
False, meta analysis have shown there is a higher death ate on MTORi
MOA of Tacrolimus? Indications?
inhibits production of IL-2, a molecule that promotes the production of proliferation of T cells
Post allogenic transpant
Eczema a T cell mediated disease
Minimal change disease
What is the mechanism behind a metabolic alkalosis associated with vomiting in a pt with severe HF on a salt restriction and frusemide?
Chloride depletion from vomiting frusemide (NaCl) results in contraction alkalosis due to secondary activation of aldosterone hence Na retention for H/K excretion.
What test can you do to differentiate from primary and central DI?
DDAVP - urine osmo does not change in primary DI.
urine osmo will respond in Central DI.
What are the common characteristics of Liddle’s syndrome?
Hypertension, short and FLK
What are the common characteristics of Gordon’s syndrome?
HT
HyperK
acidosis
Rare
What are the common characteristics of Bartter’s syndrome?
Young
Dry
Like taking lots of Frusemide
What are the common characteristics of Gittleman’s syndrome?
Thiazide effect
Low serum Mg
Low serum K
Alkaloctic pH
Urine K increased
Mycophenalate is safe is pregnancy. T/F
False.
Switch to azathioprine 3 months before conception to reduce the risks of congenital birth defects
Live kidney donation is a better option for most patients with ESKD?
True, survival 1.5-2x better than deceased donor Tx
Post kidney function is 70% of predonation? T/F
True
Pt with renal artery stenosis on ACEI and CCB. BP not controlled. Next step?
Add thiazide
If not controlled on ACEI alone, add long acting CCB, aldosterone antagonist or BB.
In unilateral renal artery stenosis, when is revascularisation (stenting/angioplasty) indicated over medical therapy alone (must meet 1 of 4 criteria)?
Short duration of BP elevation prior to Dx of renovascular disease since this is the strongest clinical predictor of a fall in BP after renal revascularisation
Failure of optimal medical therapy to control BP
Intolerance to optimal medical therapy
Recurrent flash of pul oedema and/or refractory HF
Studies have indicated there was no significant difference in medical therapy vs revascularisation, even in pts with 80% stenosis
Pt pregnant, previous VTE due to Sx. Mx during pregnancy?
Clinical surveillance preferred over thromoprophylaxis unless multiple VTEs have occurred.
Threshold for thromboprophylaxis is lowered in the post part period as there is an increased with of VTE. 2-5 x more common beyond post partum.
Minimal change disease. What? Cause?Clinical? Dx?Tx?
Nephrotic syndrome associated with atopic diseases and lymphomas.
Most common cause of nephrotic syndrome in children. 10-15% adults.
A disorder of lymphocytes which release IgG and cytokines that alter glomerular capillary permselectively.
Cause:
idiopathic
NSAID related
paraneoplastic e.g. HL
Clinical
Significant proteinuria
Dx
•Confirmed with kidney Bx
•Light and Immunofluoresecence microscopy are normal. NO immune complexes.
•Electron microscopy demonstrates characteristic fusion and effacement of podocytes (visceral epithelial cell) foot processes.
Mx
Prednisone
If relapse, consider cyclophosphamide
If relapse or gonadal toxicity with cyclophosphamide consider cyclophosphamide
If fails cyclophosphamide and cyclosporin, consider rituximab
Loop diuretic resistance is due to? Tx?
increased tubular Na reabsorption in nephron segments other than the loop of Henle.
The decreased response to the action of a diuretic that results from increased Na reabsorption on other nephron segment has been called the diuretic braking phenomenon.
Tx:
Increase loop diuretic to BD, TDS dosing if patient has partial but adequate response to dosing
A thiazide diuretic added
T/F. Changes in the charge or size of the selective barrier in the GBM is involved in the pathology of nephrotic syndrome?
True
Nephrotic urine reflects defects in the selectivity glomerular ultrafiltration
In nephrotic syndrome, what is the protein loss due to?
glomerular proteinuria characterised by increased filtration of macromolecules across the glomerular capillary wall
Idiopathic nephrotic syndrome (membranous nephropathy, minimal change diseases, focal segmental glomerulasclerosis). What is the major cause of proteinuria?
Podocyte is the major target of injury - podocyte foot process effacement, slit diaphragm disruption and depletion of podocytes.
What is the pathophy of adult onset idiopathic membranous nephropathy and FSGS?
Pathology?
Cause?
autoabs to podocyte antigens
circulating factors like soluble urokinase-type plasminogen activator receptor that activate podocyte integrins or circulating factors like cytokines or microbial products that may induce podocyte CD80
Pathology:
Focal =
What is erythropoietin produced in response to?
Synthesised in kidneys, in peritubular cells.
Erythropoietin stimulates proliferation and maturation of erythroid cells through ligand binding to the erythropoietin receptor.
Pathogenesis of contrast nephropathy?
Main mechanism of contrast induced nephropathy is intra-renal vasoconstriction.
Medicated by vasoactive mediators such as endothelin and adenosine.
Reduction in renal perfusion is caused by direct effect of contrast media on kidney and toxic effects on the tubular cells are generally accepted as the main factors in pathophys.
What is the most common organism in PD peritonitis?
Co-ag -ve S. aureus is the most common in Australia. (Staph aureus in America)
What is the most likely non-SCC malignancy in renal transplant patients?
Lymphoma
AG, normal range?
7-13 (traditionally 8-16)
Causes of Normal AG Metabolic acidosis?
Diarhhoea
RTA
- If RTA cannot be distinguished from diarrhoea, calculate urine AG
- Urine AG is +ve with NAGMA secondary to RTA
- Urine AG is negative with NAGMA seoncardy to GI losses
CA inhibitors
Hyperalimentation with TPN
Causes of High AG metabolic acidosis?
ketoacidosis
uremia (CRG)
lactic aciodis
toxins
Pt with URTI, haematuria, subnephrotic range proteinuria and mesangial depositis that stain for IgA. Dx?
IgA nephropathy
Pt with hx of recent infection (any infection, but most likely streptococcal 2-3 weeks prior), haematuria, subnephrotic range proteinuria, red cell casts and ASOT normal, glomeruli have large sub epithelial hump like deposits, elevated. Dx?
Post infectious GN
T/F. Changes in the charge or size of the selective barrier in the GBM is involved in the pathology of nephrotic syndrome?
- True
* Nephrotic urine reflects defects in the selectivity of glomerular ultrafiltration
In nephrotic syndrome, what is the protein loss due to?
- glomerular proteinuria characterised by increased filtration of macromolecules across the glomerular capillary wall
- cytokine injury to podocytes and loss of charge on GBM
Idiopathic nephrotic syndrome (membranous nephropathy, minimal change diseases, focal segmental glomerulosclerosis). What is the major cause of proteinuria?
•Podocyte is the major target of injury - podocyte foot process effacement, slit diaphragm disruption and depletion of podocytes.
What is the pathophy of adult onset idiopathic membranous nephropathy and FSGS?
autoabs to podocyte antigens
- circulating factors like soluble urokinase-type plasminogen
- activator receptor that activate podocyte integrins or
- circulating factors like cytokines or microbial products that may induce podocyte CD80.
What is the most common cause of nephrotic syndrome in adults? Causes of primary and secondary? Presentation? Dx? Tx?
Diffuse membranous glomerulopathy
Primary
- in situ immune complex disease in which the Ig of The IgG class react with constitutive or planted antigens in the outer aspect of the GBM
- mainly adults > 50 y
- 2/3 of pts undergo spontaneous complete or partial remission and 1/3 have progressive disease that may result in ESRF within 10 years
Secondary
- SLE
- Infections: Hep B, C, malaria
- malignancies
- NSAIDs
Presentation:
- Nephrotic syndrome - think Protein LEAC
- highest prevalence of renal vein thrombosis compared with other causes of nephrotic syndrome
Dx
- Kidney Bx shows diffuse thickening of the glomerular capillary wall on light microscopy and intra membranous electron dense deposits initially located in the sub epithelial aspect of the glomerular basement membrane on electron microscopy
Mx
- Depends on mild, mod, severe proteinuria
- commence on ACEI
- If proteinuria 4-8 g/d, immunosuppresive therapy with cyclophosphamide/corticosterouds or calcineurin inhibitor
- check cholesterol q1-3 months
- commence anticoagulation of symptoms of renal vein thrombosis.
What dietary modification is of most benefit in nephrotic syndrome?
Low Na diet
IgA nephropathy *GN). Cause? Epid? Clin? RF? Dx? Tx?
IgA nephropathy may primarily involve only one kidney or may be secondarily associated with other conditions such as HIV infection, chronic liver disease, IBD or coeliac disease.
Patho
•IgA nephropathy, the most common primary glomerulonephritis, is an immune complex disease in which IgA antigen-antibody complexes are deposited primarily in the mesangium.
•IgA nephropathy may primarily involve only the kidney or may be secondarily associated with other conditions such as HIV infection, chronic liver disease, inflammatory bowel disease, or celiac disease. IgA nephropathy is the renal lesion of Henoch-Schönlein purpura, a systemic vasculitis most commonly seen during childhood.
Epid
•Primary IgA nephropathy occurs at any age and has a predilection to develop in men who are white or Asian. Approximately 20% to 30% of patients have progressive disease that can lead to ESKD within 10 to 20 years of onset.
RF
•Risk factors associated with progressive CKD include younger age at onset; hypertension; proteinuria ≥1 g/24 h; elevated serum creatinine levels; low GFR; and secondary glomerulosclerosis, chronic tubulointerstitial changes, and crescents on biopsy. Persistent proteinuria (≥1 g/24 h) and hypertension are two modifiable risk factors that increase the risk of progression to advanced CKD.
Clinical
•Most patients with IgA nephropathy are asymptomatic at presentation, with only microscopic hematuria and proteinuria discovered on evaluation of the urine.
•A common presentation of primary IgA nephropathy is recurrent gross hematuria occurring synchronously with an episode of respiratory (“synpharyngitic hematuria”) or gastrointestinal infection.
•This may be associated with acute kidney injury precipitated by occlusion of tubular lumina by erythrocytes and erythrocyte casts.
•Less frequently, patients may present with the nephrotic syndrome or RPGN.
Dx
•Diagnosis is confirmed by kidney biopsy, which demonstrates mesangioproliferative glomerulonephritis with IgA-dominant mesangial immune deposits on immunofluorescence microscopy.
Mx
•Corticosteroids with immunosuppressive agents and antiplatelet agents may be beneficial in the management of primary MPGN but more than 50% of patients progress to advanced CKD.
•Treatment of secondary MPGN I is directed toward the underlying cause.
What is the most common extra-renal manifestation of PCOS?
Hepatic cysts - 94%
Mitral valve prolapse 25%
Abdominal hernia 10%
Intracranial aneurysm 8%
Colonic diverticuli
Renal transplant: What feature of acute rejection has the worst prognostic implication?
Vascular injury .
Long term survival is base don initial response to therapy.
What are the recommendations for metformin dosing based on eGFR?
eGFR =45:
- continue use
Monitor RF q 3-6 months
eGFR = 30:
- presecribe metformin with caution
- use lower dose e.g. 50% or half maximal dose
- Monitor RF q3months
- do not start new patients on Metformin
eGFR
What is the most common infection post renal transplant?
E. coli
What is calciphylaxis? Tx?
Condition characterized by calcification of arterioles resulting in ischaemia and necrosis.
Presentation:
Excruciating pain
Violaceous painful, plaque like SC nodules that progress to ischaemic/necrotic ulcers.
Tx:
Multifactorial approach. Optimal therapy unknown.
Wound care, analgesia, avoidance of trauma.
O2 therapy 2-3hrs/d or hyperbaric O2 therapy.
Correct hypercalcaemia and phosphate
- phosphate binders sevelamer (non Ca containing)
If PTH high, cinacalcet
Parathyroidectomy if uncontrolled Ca and PO4.
Increased haemodialysis.
Post infectious GN characterised by?
Nephritis: proteinuria, haematuira, oedema, HTN and AKI.
Strep pharyngitis or cellulitis 2-3 weeks prior
Ix:
MICROSCOPIC HAEMATURIA with leucs and 24 hr urinary albumin of 227 mg.
(IgA nephropathy and Sickle cell disease present with gross hematuria)
Low C3 Normal or low C4 Elevated anti-streptolysin O and anti-deoxyribonuclease B Positive streptozyme test - most useful test as measures the 5 antibodies that may be elevated with a recent strep infection: anti-streptolysin O anti-deoxyribonuclease B Anti-hyalaruronidase Antistreptokinase Antinicotinamide
Tx:
Supportive
Tx underlying infections
No evidence for steroids
What is ANCA (pauci-immune) vasculitis charcterised by?
ANCA +ve
Normal complement levels
Abscence of Ig on immunoflourescent staining of kidney biopsy
Antiglomerular basement membrane disease is characterised by normal complements. T/F
True
What is analgesic nephropathy characterized by on CT?
Papillary necrosis and calcifications in the renal papilla with irregular kidney contours and reduced size.
Due to long term use of NSAIDs, aspirin, codeine, acetominophen.
May present with flank pain, haematuria obstruction from papillary necrosis.
When is sevelamer indicated?
To reduce serum Ph in ESRF
What is Teriparatide?
Synthetic form of PTH used to treat severe OP.
CI in pts with hypercalcaemia.
Which nephrotic syndrome is most commonly associated with renal vein thrombosis?
Membranous nephropathy (disease of old) Presents with haematuria and flank pain
Image with CT, MRI, duplex US
Commence on anticoagulation to salvage renal function
Muddy brown urine suggestive of?
ATN and related to the presence of granular casts in the urine
Red urine without haematuria suggestive of?
Medications or ingestion of beets
Haematuria due to structural lesion in kidnyy or urinary tract or from abnormalities of the BM.
Grains in urine suggestive of?
Urolithiasis
What is the most likely cause of a pt with fever, rash and acute injury after starting a new medication?
Acute interstitial nephritis.
Medications account for 75% of cases - Abx, NSAIDs, PPIs
What is the classic presentation of AIN? Tx?
Fever Rash Arthralgia Peripheral eosinophilia AKI White cell casts
Tx: Cease medication Observe Renal Bx if no resolution Can consider glucocorticoids but no RCTs
What is ATN characterised by?
Hx of exposure to nephrotoxic agent or ischaemic injury from volume depletion
Urine sediment has granular casts rather than white cell cast
Tx for focal segmental glomerulosclerosis?
1st line: ACEI to reduce protinuria + glucocorticoids.
If no response, then Calcineurin inhibitore.g. cyclosporine
What is the Tx for nephrocalcinosis and hypercalcaemia in sarcoidosis?
Prednisone.
HyperCa and Hypercalciura are common manifestations of sarcoid occurring in 10-20 and 30-40% of patients respectively.
Nephroclacinosis is the deposition of calcium in the kidney parenchyma occurring in 50% of pts with sarcoid who have renal dysfunction.
Thiazide diuretics CI as increase Ca retention.
Loop diuretics increase Ca excretion however not indicated in the Tx.
How is morphine cleared?
Metabolised to renally excreted glucuronide metabolites (M6G abd M3G).
M6G is active and accumulates in the CNS.
M3G lacks analgesic activity but may cause hyperglycaemia and allodynia.
Causes of nephritic syndrome?
Nephritic syndrome is usually proliferative disease: order of following diseases range from severe acute to indolent
Diffuse proliferative GN Cresentric GN - think ANCA associated Focal proliferative GN Mesangio-proliferative GN - think IgA nephropathy/HSP
Cause of mixed nephritic and nephrotic syndrome?
Membranoproliferative GN (aka mesangiocapillary)
- think immune complex disease e.g. SLE, endocarditis, HCV and
- thrombotic microangiopathy e.g. TTE/HUS/HELLP/DIC
- cyroglobulinaemia
Complement disorders
What 3 test do you order when considering nephritic syndrome?
Anti-GBM
ANCA
C3
Anti-GBM (Goodpastures): anti-GBM +ve ANCA -ve C3 normal Immunofluorescence shows linear pattern of Ig and C3 (becaus it is on the BM!)
ANCA (Wegeners’, MPA, Renal limited vasculitis):
Anti-GBM -ve
ANCA +ve
C3 normal
IF shows pauci-immune pattern with absent or sparse Ig and C3
(pauci immune pattern will also be seen in non-immune diseases such as malignant HTN, TTP/HUS, atheroembolic disease and scleroderma)
Immune complex mediated disease (GN with granular IgG):
Anti-GBM -ve
ANCA -ve
C3 low
IF shows granular pattern
e.g. SLE, cryoglob, endocarditis associated GN, Idiopathic, post infectious GN, Drug induced
Which immune complex mediated diseases (IF shows grnaular pattern) does not cause a low C3?
HSP
IgA nephropathy
What are the 4 major causes of nephrotic syndrome? (MMAF)
Membranous - most common type in older adults
Minimal change disease - younger pts, hx of atopy
Amyloidosis
FSGS
Membranous disease. Cause? Electron microscopy (EM) shows?
Nephrotic syndrome
Most common type in older adults.
Causes:
Idiopathic
Secondary - drugs, HBV, malignancy
EM demonstrates a thickened BM (hence membranous)
Amyloidosis. Types. Cause?
AA or AL.
AA associated with chronic inflammation.
AL typically presents in older ppl and may or may not be associated with myeloma.
What is the role of NaBicarb in the Tx of chronic metabolic acidosis in the setting of chronic renal failure?
Reduced progression of renal disease
Fibromuscular dysplasia.
What, Presentation. Tx?
Non-atherosclerotic ateriopathy affecting the mid to distal renal arteries (less commonly cerebral vessels).
Presentation:
Young females with early onset HT
Tx:
Treated with angioplasty
What are the extrahepatic manifestations of HCV?
Glomerulonephritis (MPGN most common) Thyroiditis Insulin resistance and DM Porphyria cutaena tarda Lichen planus Vitiligo Seronegative arthritis Cryoglobul lymphoproliferative disorders
What are the extrahepatic manifestations of HBV?
PAN
Membranous nephropathy or MPGN
Serum sickness like arthritis dermatitis
What is the earliest physiological change seen in diabetic nephropathy?
Increased GFR then
microalbuminaemia, HT then
Proteinuria, nephrotic syndrome and decreased GFR
Renal denervation, MOA in Tx of resistant HT?
Peripheral vasodilation
What is the primary cell involved in renal allograft rejection?
CD4 T lymphocytes.
Main target of calcineurin inhibitors and IL-2 antagonists.
Describe the process of CD4 T cell activated T cell.
CD4 T cell -> IL 2 activates T cell -> release TH1, TH2, TH17 and Treg.
TH1 produces IFN-y and IL-2
TH2 produces IL 4,5 and 13
TH17 produces IL17,21 and 22
T-reg produced IL-10 and TGF-B
What does mannitol and cerebral salt wasting cause?
Hyponatraemia
Pt with diabetic nephropathy presenting with oedema and weight gain. ACEI, CCB and frusemide. Tx?
Na restriction would be key to improve oedema.
Fluid restriction.
Add thiazide diuretic.
MOA of acetazolamide?
carbonic anhydrase inhibitor, acts on proximal tubule. Weak diuretic and most of the fluid and Na will be reabsorbed further down the tubule.
MOA of mannitol?
osmotic agent. Acts on proximal tubule.
MOA of aldosterone antagonist?
Inhibits Na absorption in distal tubule and spares K.
ADH antagonist. Examples. MOA? Indication?
Demeclocycline
-SIADH resistant to fluid restriction
Tolvaptan
-euvolaemic or hypervolaemic hyponatraemia.
Acts on collecting duct.
What is the strongest single biochemical predictor of mortality in dialysis patients?
Albumin
Marker of mortality.
Decreases with poor nutrition and chronic inflammation
Primary benefit of EPO in CRF?
Improvement in QOL.
No mortality benefits.
What is the most common non-SCC malignancy in renal transplant patients?
Lymphoma
In which part of the kidney does urine acidification occur?
Collecting duct
NH3 secreted in urine along the collecting duct and protonated and trapped as NH4+ excreted in urine.
HUS. Ix results?
Microangiopathic haemolytic anaemia.
Schistocytes = fragmented Red cells, >1% strongly suggestive of HUS/TTP
Thrombocytopenia
Renal involvement - thrombotic microangiopathy -> elevated Cr
What happens to the aldosterone:renin ratio is renovascular disease?
Reduced aldosterone to renin ratio
What happens to the aldosterone:renin ratio in primary aldosteronism and CAH?
Aldosterone:renin ratio > 30
ALdosterone driven process
direct renin assay -> renin suppressed
What is the Cockcroft-Gault equation?
Estmation of CrCl, not GFR
Uses age, sex, weight
= (140-age) x weight/ 0.814 x S..(umol/L)
Overestimates GFR in obese people
Especially inaccurate over 60 ml/min
CrCl is proportional to the patient’s ideal body weight
Plasma levels of Cr are lower in elderly patients and pts with profound muscle wasting
CrCl correlates inversely with plasma Cr therefore doubling plasma Cr reflects s reduction in Cl by half
Drugs such as Trimethoprim, cimetidine and probenacid inhibit tubular secretion and results in decreased Cr Cl
DDx of hypokalaemic metabolic alkalosis:
Hypertensive
Normotensive
Hypertensive (suppressed renin):
Hyperaldosteronism
Pseuo-hyperaldosteronism
- liquorice
- ectopic ACTH
- Syndrome of apparent mineralocorticoid excess
- Liddle syndrome (AD, gain of function in ENaC -> Na absorption and K secretion). Causes HT.
Normotensive (elevated renin):
Surreptitious vomiting
Diuretic abuse
Na wasting tubolopathies
The urine Cl can narrow the DDx
- low urine Cl suggest normal renal tubular function therefore surreptitious vomiting or diuretic abuse.
- high urine Cl suggest salt wasting tubulopathy e.g. Bartter’s or Gittleman’s and diuretic abuse
Metabolic alkalosis. Causes?
Causes with low Cl- vs. low K-
Accumulation of HCO3 due to: acid loss alkali aministration intracellular shift of H+ (hypokalaemia) HCO3 retention
Common causes with low Cl-:
GI acid loss - vomiting, NGT suction
diuretics
diarrhoea
Low K:
Primary hyperaldosteronism
Drugs e.g. liquorice, laxative abuse
Barter’s, Liddle’s, Gittleman’s
Which enzyme is responsible for the conversion of 2-phosphoglyverate to phosphoenolpyruvate (penultimate step of glycolysis)?
Enolase
Which enzyme is responsible for catalysing the interconversion of pyruvate and lactate?
Lactic acid dehydrogenase
Which enzyme is responsible for phosporylation of fructose-6-phosphate in glycolysis?
Phosphofructokinase
Which enzyme breaks down a phosphodiester bond>
Phosphodiesterase
How can you prevent osmotic demyelination associated with correction of hyponatraemia?
Limiting correction of chronic hyponatraemia to
In PCOS what is the main cause of RF?
Increase in the size of existing cysts which causes
- percystic fibrosis
- HT
- tubular obstruction
What is the best predictor of RF in PCOS?
HT
what is calcitriol
(aka 1,25‑dihydroxycolecalciferol and 1,25‑dihydroxyvitamin D3) ?
Activated Vitamin D
- increases Phosphate and Ca absorption from the gut
What are the limitations of eGFR?
as GFR falls, rise in serum Cr partially opposed by enhanced proximal tubular Cr secretion.
That is why there is a slight increase in serum Cr with the initial decline in GFR in early renal disease.
Cr is not accurate in acute kidney injury as it takes time for Cr production and the changing GFR to equilibrate.
ATN: Causes Ix Tx Prognosis
Most common cause of intrinsic kidney disease causing AKI.
Causes:
Ischaemic event - hypovolaemia, hypoxia
Nephrotoxic agents - abx, amphotericin, tenofavir, pentamidine, NSAIDs, dye, Csiplating, carboplatin, Ifosfamide, heavy metals, lead
Ix:
Urine - muddy brown casts and high urine sodium with fractional excretion > 2%.
Otherwise urine is often bland.
Tx:
Maintaining adequate perfusion pressure
Discontinuing drug
Adjust renal dose meds
Prognosis:
Depends on original insult.
If mild, quick recovery.
Severe can lead to dialysis dependent
AIN:
Cause
Presentation
Typically caused by a hypersensitivity reaction to a medication.
Causes:
Drugs e.g. Abx, Antivirals, NSAIDs, analgesics, PPIs, 5 aminosalicylates.
MM
AI diseases
Presentation: Presentation can be variable depending on drug. Classic (10% of ppl): Fever rash Eosinophilia Elevated sCr Usually occurs 7-10 days after drug exposure
Ix:
Urine: leucocytes and leucocyte casts with negative urine cultures and erythrocytes
Tx:
Stop drug
Evidence for corticosteroids is limited. Considered if prolonged or severe AIN.
Is used, more effective if initiated earlier.
Urgent dialysis indications?
Intractable Hyperkalaemia Severe metabolic acidosis Pericardial rub Intractable fluid overload neurological signs
Most common AE of erythropoietin stimulating agents (ESA)?
HT, 20-30%.
Target Hb 100-115.
NOTE:
Erythropoeiten does not improve CVS outcomes.
Trials have demonstrated a higher incidence of thromboembolic events, stroke in T2DM, and faster progression to need for dialysis.
What are the normal values for plasma osmolality, urine osmolality?
Plasma osmolality 283-293
Urine osmo >750
Central DI:
Post fluid restriction:
Plasma osmolality
Urine osmo
Post DDVAP:
urine osmo
Post fluid restriction:
Plasma osmolality >293
Urine osmo 750 (Normal)
Nephrogenic DI:
Post fluid restriction:
Plasma osmolality
Urine osmo
Post DDVAP:
urine osmo
Plasma osmolality >293
Urine osmo
Chronic polydipsia:
Post fluid restriction:
Plasma osmolality
Urine osmo
Post DDVAP:
urine osmo
Plasma osmolality
Partial nephrogenic DI or Primary polydipsia: Post fluid restriction: Plasma osmolality Urine osmo
Post DDVAP:
urine osmo
Plasma osmolality 750 (Normal)
What is Cinacalcet?
Indication?
Mimics stimulatory effect of Ca on the Calcium sensing receptor (CaSR) with the aim of inhibiting PTH secretion.
Cinacalcet lowers PTH and serum Ca in concetration dependent manner.
No evidence for mortality or CVS events
Causes of secondary HT?
Phaeochromocytoma - elevated metanephrines Oestrogen contining OCP - normal renin and aldosterone level Primary aldosteronism - renin suppressed (renin
Membranous nephropathy:
Presentation
Most common cause of nephrotic syndrome in whites and older adults.
Presentation: 80% nephrotic syndrome 50% microhaematuria Renal function usually normal Non specific ANA pattern may be associated
Haemodialysis targets?
Treat acidosis
- mortality benefit of treating acidosis
- bicarb supplements slow CKD progression
Oral phosphate binder
- reduce serum phosphate
- high phosphate levels in chronic renal failure infers worse prognosis
Low phosphate diet does not work.
Calcimemtics improve biochemical markers but does not improve overall survival.
Mechanism of aminoglycoside nephrotoxicity?
toxicity from accumulation and retention of aminoglycaside in the proximal tubule cells -> after several days develop defect in renal concetrating ability, mild proteinuria, hyaline and granular casts -> ATN.
Impairment of renal function almost always reversible given capacity of tubular cells to regenerate.
What is the most sensitive marker for early kidney disease?
Timed albumin/Cr ratio over 24 h.
Gold standard.
Spot ACR validated for detecting microalbumniuria and easier to use in practice.
3 days post renal transplant. pt has been oliguric since. MAG3 scan shows uptake of tracer in kidneys indicating good perfusion but no evidence of tracer excretion. Dx?
ATN
In a pt with proliferative GN, which finding on Bx is most consistent with poor response to immunosuppresants?
Advanced glomerulosclerosis.
Glomerlusclerosis = scarring
Will not be reversible with immunosuppresion.
Cyclosporine and tacrolimus toxicity?
HT
- caused by renal vasoconstriction and Na retention
- usually develops within the first few weeks of therapy.
Neurotoxicity
- mild tremor common 35-55%
- rarely severe headache, visual abnormlaities, seizures
Posterior reversible encephalopathy syndrome (PRES)
- confusion, headache, altered LOC, visual changes, seizures
- characteristic posterior cerebral white matter oedema on neuroimaging
Diagnostic guidelines for ADPKD?
15-39y
>= 3 cyst unilateral or bilateral, spec and PPV 100%
40-59 y
>= 2 cysts in each kidney
60y or older
>=4 cysts in each kidney
Diagnosis of ARPKD?
cystic dilatation of the renal collecting ducts, not the whole nephron like ADPKD
US: bilateral echogenic kidneys with poor corticomedullary differentiation
Dx of medullary sponge kidney?
Malformation of the terminal collecting ducts in the pericalyceal region of the renal pyramids.
Cysts don’t involve the cortex.
US: uniformly echogenic corticomedullarly junction, non specific
What is tuberous sclerosis?
Inherited mucocutaneous disorder
Benign harmatomas of multiple organ systems
Most frequent renal manifestation are angiomyolipomas
MOA of oxybutynin?
Inhibits action of ACh on smooth muscle -> strong antispasmodic effect therefore: increases bladder capacity decreases uninhibited contractions delays desire to void decreases urgency and frequency
Dialysis. Contraindications. Absolute vs. relative
Absolute:
documented loss of peritoneal function or
extensive abdo adhesions that limit dialysate flow
Absence of suitable assistant if pt is incapable of performing PD
uncorrectable mechanical defects e.g. irreparable hernia, bladder extropy
Relative: Fresh intra-abdominal foreign bodies Peritoneal leaks morbid obesity IBD Abdominal wall infections severe malnutrition frequent episodes of diverticulitis
Lupus Nephritis. Stages and Tx?
Stage I: Minimal Messangial GN (mild, no symptoms)
- normal in light microscopy
- immune deposits with IF microscopy and/or electrodense deposits by electron microscopy.
- Good prognosis
Stage II: Mesangial Proliferative GN (microscopic haematuria/proteinuria)
- mesangial hypercellularity on light microscopy
- mesangial immune complex deposits
- good prognosis
Stage III: Focal proliferative GN (Haem, protein +/- HTN)
- Involves =50% as above
Stage V: Membranous GN (nephrotic syndrome, microscopic haem + HTN)
- characterised by thickening of the BM
- subepithelial immune-complex deposits
- Can occur in combination with class III or IV
- Bad prognosis without Mx
Stage VI: Advanced sclerosing GN (progression, bland sediment)
- >=90% of glomeruli globally sclerosed without residual activity
Progressive unresponsive GN
Tx:
Stage I and II
- ACEI pr ARBs for proteinuria
- corticosteroids ot quinine in extrarenal manisfestations
Stage III, IV and V
- immunosuppresive agents (cyclophosphamide, mycophenalate and azathioprine) to induce remission, prevent relapse and reduce risk of progression
Post renal tranplant. Recurrence rates of GN?
High risk of recurrence rates and graft loss. Good pastures 100% Mesangiocapillary type II 80-90% IgA nephropathy 40-50% FS sclerosis 20-30% Meangiocapillary Type 1 20-30% And basically all the other AI diseases
Post renal tranplant. Recurrence of metabolic and other diseases?
Diabetic nephropathy 100% Fabry's disease 100% Oxalosis 90-100% Mixed essential cryoglobulinaemia 50% Amyloidosis 30% Scleroderma 20%
What is the most common cause of death with a functioning graft post renal transplant?
Number one cause is CVS.
Followed by malignancy then infection.
CVS:
50x higher annual risk
3 fold incidence of CHF
3 fold incidence of strokes sue to cerebral haemmorhage
Post renal tranplant infections: 1 month 2 months 3 months > 6 months
1 month: Viral - HSV Bacterial- pneumonia, wound infections, catheter related candida Onset of Hep/C
2 months:
Viral - HSV, onset of CMV, EBV, shingles, RVS, adenoviurs
Bacterial - nocardia, listeria, Tb
Fungal - PJP, aspergillus, crypto later on
Parasitic - strongyloides, Toxoplasma, Leishmania, Trypansoma cruzi
3 months:
Viral - CMV retinitis or colitis, Papillomavirus, PTLD, hepb/c
Bacterial - Listeria, Tb
Fungal - cyptococcus
> 6 months:
Fungal - Cyropto
Viral - CMV retinitis or colitis, VZV, Parvovirus B 19, HHV-8
Polyomavirus (BK, JC)
bacterial - Listeria, Tb
Associated with malignancy e.g. EBV, papillomavirus, HSV,
Unusual sites e.g. paraveterbral abscess
BK viurs nephropathy. Recipient risk factors?
Tx?
Infection a result of immunosuppression
RF: Older Male Caucasian DM CMV infection prior tubular injury Seronegativity Abscence of HLA-C7
Tx:
If BKV viraemia (in blood only), decrease immunosuppresion
If BKV in kidney Bx
- Tx with Leflunomide (mitochondrial enyme and TKI)
Antibiotics: cipro or Cidofovir
What is the largest single cancer cause of death in Australia?
Metastatic SCC
What is the most common golmerular disease worldwide?
IgA nephropathy
Frusemide. MOA?
Inhibits Na-K-2Cl transporter
Barter is due to a defect of Na reabsorption here.
Can Frusemide cause hyponatraemia?
No
Gittleman’s syndrome. Where is the problem on the renal tubule?
Distal convoluted tubule (DCT) where Na is reabsorbed by apical NaCl cotransporter.
Thiazide diuretics inhibit the NaCl cotransporter.
Gittleman’s is due to a defect in Na reabsorption here.
RTA is characterised by a normal gap (hyperchloraemic) acidosis despite a preserved GFR. What are the 3 types? Tx?
Hypokalaemic:
Type 1
- distal
- inability to secrete H+ therefore urine pH >5.5
- nephrolithiasis, nephrocalcinosis, sjogren, SLE, PBC, AI hep.
Tx: Alkali and K replacement
Type 2
- Proximal tubule
- inability to reabsorb HCO3- therefore pH
Tick bite (Lyme disease). Forestry worker. Erythema migrans - rash that is cellulitis. Tx for it?
Doxycyline
Viral Meningitis. Most common cause of aseptic memingitis?
Most common bacterial meningitis?
Most common meningitis in immunocompromised, neonates, >50y?
Gram-ve bacilli?
Viral:
Enterovirus
Bacteria:
Strep pneum
Immuno compromised etc:
Listeria
Gram -ve bacilli
- head
Refer to MKSAP
Empirical Tx of meningitis?
Dex + Ceftriaxone
If immunocompromised, >50 years, patients with a history of hazardous alcohol consumption, or patients who are pregnant or debilitated, to cover Listeria, add Benpen.
Add Vanc if ?MRSA
How can you distinguish Gittleman’s syndrome from barter’s?
hypomagnesemia and hypocalciuria in Bartter’s
Renin is secreted by?
Erythropoiten is secreted by?
Renin = cells in macular densa
Erythropoiten secreted by granular cell in the peritubular capillary bed of the renal cortex.
TRPC6 mutation associated with?
cation channel dysfunction associated with FSGC
Fanconi syndrome?
Disease of tubular dysfunction.
Presentation:
Aminoaciduria
Type 2 RTA
Rickets
NO GLOMERULAR involvement
Renal transplant. Graft survival rates of first degree relative donors are greater than deceased?
True, 5-7% greater survival at 1 year
The dose of dialysis is defined as?
The fractional urea clearance.
The efficiency os the dialysis depends on the counter current flow rate of the dialysate.
What is the pain associated with urinary tract obstruction due to?
Increased renal blood flow -> distends collecting system or renal capsule.
Which test is the GOLD standard for the diagnosis of renal vein thrombosis?
MR venography is the most sensitive and specific non-invasive test.
Contrast venography is the gold standard but is invasive.
Which finding on urine microscopy is suggestive of a cholesterol emboli?
Eosinophiluria
Treatment for Good Pasture’s?
IV Methylpred
Cyclophosphamide
Plasmaphoresis
Good[astures and Wegner’s have similar presentation of renal and pulmonary involvement. Differentiate by ANCA and anti-GBM abs
Most common cause of nephrotic syndrome in adults?
Diabetic nephropathy.
o Altered basement membrane composition with loss of heparan sulfate that forms the negatively charged filtration barrier
o Mesangial matrix expansion
o Vascular changes with hyaline and hypertensive arteriosclerosis
1st line therapy for pul HT?
Endotehlin receptor antagonsit e.g. bosentan or ambisentan
