Renal Flashcards
Why does nephrotic syndrome lead to a hypercoaguable state?
- loss of lower molecular weight anticoagulants and fibrinolytics in urine (protein C, S, anti-thrombin)
- reduced oncotic pressure => increased hepatic production of procoagulants (e.g. clotting factors)
- increased risk of DVT & renal vein thrombosis (membranous nephropathy in particular is associated with renal vein thrombosis)
- consider anticoagulation with warfarin when serum albumin <20
- loss of antithrombin III in urine also drives platelet activation
What is ADAMTS13 associated with?
TTP (thrombotic thrombocytopenia purpura)
- caused by severely deficient activity of the ADAMTS13 protease, typically with an activity level <10%
- ADAMTS13 cleaves newly synthesized ultralarge von Willebrand factor (VWF) multimers attached to the endothelial surface that are responsible for formation of platelet microthrombi.
- Most commonly ADAMTS13 deficiency is due to autoantibodies againt ADAMTS13
Management of lupus nephritis
Class III & IV lupus nephritis requires inducation & maintanence immunosuppression
For induction - steroids or cyclophosphamide
Steroids - IV methylpred 500-1g for 3 days; pred 1mg/kg/day then wean to smaller maintanence dose
Cyclophosphamide - IV fortnightly for 3months or daily. IV less toxic due to smaller cumulative dose
Maintanence of remission
- mycophenolate or azathiopurine
- mycophenolate is better but teratogenic
- maintanence Rx for 2 yrs
What is the pathogenesis of IgA nephropathy?
-due to immune complex deposition
-increase in circulating galactose deficient IgA1 (likely provoking antigen)
-production of anti-IgA1 Abs (either IgA or IgG classes)
-immune complex deposition in mesangium & skin
-immune complexes in mesangium cause local immune activitation & injury
Blood and urine findings in AIN
Urine:
- characteristic sediment of red cells, white cells, white cell casts
- eosinophiluria - eosinophils > 1% urinary white cells. Associated with AIN, however, does not have the specificty or sensitivity to diagnose or exclude diagnosis of AIN
- variable degree of proteinuria (mild - moderate increase) ** except in NSAID induced membranous or minimal change
Bloods
- elevated creatinine
- 25-30% peripheral eosinophilia
Causes and features of type 2 proximal RTA
- impaired re-absorption of HCO3 at proximal nephron (often due to abnormality in the Na / HCO3 cotransporter)
- moderate non-anion gap metabolic acidosis (less severe than type 1 RTA because alpha intercalated cells in distal nephron can still excrete H+)
- serum bicarb 12 - 20
- urine pH usually < 5.3
- hypokalaemia ALKALI therapy worsens hypokalaemia in type 2 RTA
- hypocalcemia
- causes - monoclonal gammopathies (myeloma) ; Fanconi’s syndrome ; drugs (carbonic anhydrase inhibitors - acetazolamide, tacrolimus; tenofovir; ifosfamide), genetic causes - galactosemia, glycogen storage disease (type 1), Wilson’s; heavy metals (lead, mercury, copper); vitamin D deficiency ; renal transplant ; paroxysmal nocturnal haemoglobinuria
- complications: growth failure, osteomalacia / rickets
- management - alkali therapy -> however this worsens hypokalaemia. Potassium citrate is a must
What are the contraindications and adverse effects associated with ESA?
Contraindications - active malignancy (EPO increases risk of recurrence or progression of malignancy) and recent stroke
Increased risk of fatal and non-fatal stroke associated with EPO
Adverse effects
- Hypertension - most common. Especially with rapid Hb rise. Can occur independent of target Hb. 20-35% of pts with develop an elevation in DBP of 10mmhg or more. About 1/3 of patients started on EPO will require commencement of antihypertensive therapy. Can progress to hypertensive encephalopathy.
Possible mechanism of HTN - EPO receptors expressed on vascular endothelial and smooth muscle cells -> may trigger vasoconstriction
Can develop as early as 2 weeks after starting ESA, but onset may be delayed for 4 months or more
- Other side effects - flu-like symptoms, bone pain, mylagias, fever, rash, stroke, vascular access loss
- Pure red cell aplasia - rare condition, profound anaemia, very low reticulocyte count, other cell lines normal. Elevated serum transferrin saturation and ferritin (low utilisation). Was associated with certain brands of EPO which are now unavailable.
IgA nephropathy summary
PTH & vitamin D physiology in CKD
if PTH elevated in CKD - first give phosphate binders, then give calcitriol (if Ca is ok), then cinacalet (only PBS funded in dialysis patients), then parathyroidectomy (big surgery; may not be tolerated in dialysis patients)
Start treating when PTH is 2-10 x ULN
PTH > 100 is very concerning
Compare types of renal tubular acidosis
Clinical presentation of IgA nephropathy
-Most common (50%) - episodes of gross haematuria (cola or tea coloured), repeated episodes accompanying or just after URTI, sometimes after strenuous exercise or tonsillectomy. Typically first episode <40 yrs.
Associated flank pain and low grade fevers
- 30% patients may present with microscopic haematuria & proteinuria
-10% will present as a RPGN - with oedema, hypertension, haematuria, renal failure
- malignant hypertension is a rare presentation
- AKI also rare presentation
- can present as advanced CKD as may be asymptomatic
Predictors of prognosis in IgA nephropathy
- Degree of renal impairment (Cr) predicts progression to ESRF. If Cr > 150, risk of ESRF at 7 yrs. is 70%
- Hypertension predicts risk of ESRF or death
- Proteinuria is the most important predictor of renal outcome
Proteinuria in combination with hypertension is associated with worse outcome
Sustained proteinuria > 1g / day - associated with increased risk of ESRF, dialysis or death
Proteinuria <1g/day is indicative of near-remission with treatment and reduced risk of ESRF, dialysis or death
How is acid / base homeostasis maintained in the proximal convoluting tubule?
- Carbonic anhydrase type 1 lives in the brush border (shark) - breaks down HCO3H to water and CO2 so it can be absorbed by the PCT cells
- CA type 2 is inside the PCT cells - catalyses the reaction in the other direction to reform HCO3H
- A sodium-bicarbonate cotransporter quickly whisks away the HCO3-
- The lonely H+ is excreted in exchange for a sodium ion
Clinical presentation of AIN
- 50% oliguric and 50% non-oliguric AKIs
- asymptomatic OR nausea, vomiting, malaise
- allergic symptoms 30%
- fever, rash and eosinophilia - only 10% patients have full triad
- symptoms classically develop 3-5 days after introduction of offending agent BUT can be lag of > 1 yr for NSAIDs
How is acid / base homeostasis maintained in the distal convoluted tubule?
- CA helps shift HCO3 into cells (like in the PCT)
- Once there, the H+ is actively transported out by TWO special channels
- One uses K+
- The HCO3 is transported into the blood via exchange with Cl-
- There are 2x Cl- channels that help the Cl- get back into the blood, so it doesn’t get trapped in the cells
- One uses K+
There’s also the Na+ / K+ ATPase
- One uses K+
What are the adverse effects of tolvaptan?
Adverse effects
- hyponatremia - increase dose or drink less
- Hypernatremia - drink more or reduce dose
- polyuria and nocturia (low salt / protein intake at night to reduce nocturia)
- small decline ine GFR - up to 6-8% accepatble
- polydipsia
- hypovolemia and AKI if not adequate oral intake and if using in combination with other diuretics
- LFT derangement in 5% - monitor LFTs every 18 months
Causes and features of type 1 distal RTA
-impaired H+ excretion in distal nephron (therefore impaired NH4+ excretion in collecting tubules)
- due to decreased H+ ATPase (proton pump) activity or increased luminal membrane H+ permeability
- severe non-anion gap metabolic acidosis
- plasma bicarb can be < 10
- urine pH > 5.5 (unabel to acidify)
- hypercalciuria => renal stones
- hypocitraturia => renal stones
- hypokalaemia => IMPROVES with alkali therapy
- positive urinary anion gap ; urinary osmolality gap < 150 - distal RTA
- complications - growth failure, hypokalaemia, renal stones, osteoporosis
- management - alkali therapy, potassium salts (e.g. potassium citrate) if hypokalaemia persists
- causes
1. Most common is autoimmune diseases - Sjogren’s, AIH/PBC, SLE, RA
2. Drugs - lithium, amphotericin B, ifosfamide, ibuprofen
3. hypercalciuric conditions - hyperpTH, vitamin D intoxication, sarcoidosis, idiopathic
4. other - obstructive uropathy, renal transplant rejection, WIlson’s disease, genetic defects
Causes and features of hyperkalaemic type 4 RTA
- Aldosterone is the main hormone responsible for K excretion
- type 4 RTA is caused by hypoaldosteronism or increased aldosterone resistance
- voltage dependent RTA - reduced distal Na delivery due to reduced intake or decreased proximal tubular Na reabsorption
- typically MILD non anion gap metabolic acidosis
- serum HCO3 is variable (typically > 17 in hypoaldosteronism)
- urine pH is also variable (pH < 5.3 with hypoaldosteronism or > 5. with voltage defects)
- hyperkalaemia
Causes
- reduced aldosterone production
1. Hyporeninemic hypoaldosteronism (most common) - due to CKD (especially diabetic nephropathy), NSAIDs, GN, calcineurin inhibitors. Reduced plasma renin activity, low aldosterone levels, normal cortisol levels
2. Drugs - ACEi, heparin, LMWH
3. Primary adrenal insufficiency - low aldosterone & cortisol, increased plasma renin activity due to volume depletion and hypotension
4. Severe illness
5. inherited - congenital isolated hypoaldosteronism, pseudohypoaldosteronism type 2 / Gordon’s syndrome
-increased aldosterone resistance
K+ sparing diuretics, trimethoprim
-voltage-dependent RTA
severe hypovolemia, obstructive uropapthy, lupus nephritis, sick cell disease
Management
- treat underlying disorder
- fludrocortisone for hyperkalaemia; may worsen hypertension and oedema
What are the causes of AIN?
- Most common cause is drugs, especially antibiotics.
-penicillins
-cephalosporins
-rifampicin
-ciprofloxacin and other quinolones
-diuretics - esp thiazide
-PPI
-NSAIDs
-Allopurinol
-5-ASA
-Methamphetamine
-checkpoint inhibitors - Autoimmune disease 10-20%
SLE, sarcoidosis, Sjogren’s, GPA - Infections 4-10%
Legionella, mycobacterium, streptococcus, CMV, Leptospira, CMV - TINU (tubulointerstitial nephritis and uveitis syndrome)
Prognosis in lupus nephritis
Predictors of poor prognosis
- paediatric onset
- male
- non-white ethnicities - African American / Hispanic groups
- neuropsychiatric lupus
- proteinuria >4g/day at diagnosis
- frequent relapses
- elevated creatinine at presentation
- failure to achieve remission
Histologic characteristics
-crescenteric GN
-TMA
-extensive tubulointerstitial involvement
-high chronicity index on biopsy
Serologic characteristics
-high titre dsDNA antibodies
-persistently low complement levels
-high titre C1q antibodies
-antiphospholipid antibodies or antiphospholipid syndrome
Management and prognosis of AIN
Drug-induced AIN
- stop offending agent
- if rapidly progressing to dialysis - corticosteroids
- mycophenolate if not responding to 8-12 weeks of steroids
- most pts recover after offending agent ceased. Persistent elevation in creatinine to 150 seen in 40-70% pts, depending on severity of AKI.
- prognosis worse with NSAID related AIN
Non-drug induced AIN
- treat underlying disease process
- prognosis worse in autoimmune associated AIN - progression to dialysis is common, but only 10% remain dialysis dependent
What occurs to Vitamin D & Ca in nephrotic syndrome?
- vitamin D binding protein is lost in urine; 25-hydroxyvitamin D is excreted with it
- calcitriol (1,25 dihydroxyvitamin D) levels may be normal or reduced
- can have low serum total calcium concentration with hypoalbuminaemia; however ionised calcium concentration is unaffected
- if low calcitriol and low ionised calcium, may need cholecalciferol replacement
What are the findings on renal biopsy in diabetic kidney disease?
Abnormalities in order of progression
1. Thickened glomerular basement membrane - occurs early, can occur within 2 yrs of T1DM diagnosis
2. Mesangial cell proliferation (TGF beta driven)
3. Mesangial matrix expansion (TGF beta driven) - can be diffuse or nodular. Nodular = Kimmelstiel-Wilson nodules
4. Podocyte injury
5. Glomerular sclerosis
6. Tubulointerstitial fibrosis (usually occurs after initial glomerular lesions; final common pathway mediated progression from advanced CKD to ESKD)
Why does creatinine increase with RAAS blockade? How much of a rise in creatinine is acceptable after initiation of ACE inhibitors?
As per KDIGO guidelines, continue ACEi/ARB unless serum creatinine rises by > 30% within four weeks after initiation of treatment / increase in dose.
Reduction in eGFR / rise in creatinine, which is usually moderate 5-25%, but can be severe > 30%, can be seen in patients with bilateral renal artery stensosis, hypertensive nephrosclerosis, CCF, PKD, CKD, after commencing ACEi/ARB.
In these disorders, intraglomerular perfusion pressure is reduced. Therefore, eGFR is maintained (in part) by angiotensin II mediated vasoconstriction of the efferent arteriole. Block RAAS -> reduce efferent arteriole constriction that was maintaining eGFR -> creatinine rise
Creatinine therefore begins to rise in a few days after ACEi / ARB is started because levels of ATII are rapidly reduced
Indications for renal biopsy in lupus nephritis and classic histopathological findings
- renal bx should be performed in most pts with SLE who develop renal involvement, to determine histologic class and therefore determine Mx
- histologic class can change - therefore any clinical change may warrant consideration of bx
IF / histopath
- glomerular deposits that stain primarily for IgG, but also IgA, IgM, C3 and C1q “full house immunofluorescence pattern”
Full house pattern also seen in HIV, IE, post strep GN
- Glomerular deposits (mesangial, subendothelial, subepithelial) and extraglomerular deposits (tubular basement membrane, interstitium, vessels), tubuloreticular inclusions in glomerular endothelial cells
Tubuloreticular inclusions also seen in HIV nephropathy (although this is typically collapsing FSGS) and people treated with alpha-interferon
Indications for renal biopsy in suspected IgA nephropathy and findings on immunofluorescence & histopath
Indications for renal biopsy
- needed to confirm diagnosis, however, typically only performed in setting of rapidly progressive or severe disease
- persistent proteinuria > 1g / day
- new hypertension or significant rise over baseline BP
- elevated creatinine
IF - immune complex deposition (IgA or IgG in mesangium)
Light microscopy - mesangial hypercellularity and matrix expansion
Histopath - immune complex pattern, hypercellularity, glomerular sclerosis, interstitial fibrosis, formation of crescents due to proliferation of epithelial cells
Pathogenesis of scleroderma renal crisis
- Occurs in up to 20% of pts with diffuse cutaneous systemic sclerosis
- most comonly in first 5 years after diagnosis
- underlying mechanism - thrombotic microangiopathy / vascular changes in small arteries of the kidney
- intimal proliferation and thickening, narrowing and obliteration of vascular lumen, concentric onion-skin hypertrophy
Risk factors for scleroderma renal crisis
- more common in first 5 years after diagnosis of diffuse cutaneous systemic sclerosis
risk factors
-> diffuse cutaneous systemic sclerosis, especially if rapidly progressive
-> anti RNA polymerase III Abs
-> glucocorticoid use - > 15mg prednisolone per day
Clinical presentation of scleroderma renal crisis
- acute onset renal failure
- abrupt onset moderate - marked hypertension in 90% patients, associated with headache & blurred vision, retinopathy (including haemorrhages and exudates), encephalopathy complicated by seizures
- new diastolic hypertension (85%)
- mean peak blood pressure of 180/100mmHg
- urine sediment is usually normal. Proteinuria 0.5-1g/day may be present in pts with pre-existing hypertension. GN is not a feature of SRC - microscopic haematuria and cell casts are uncommon
- 10% of SRC is normotensive, although BP may be higher than baseline. Worse prognosis due to delayed recognition. Normotension in SRC may suggest cardiac failure.
Management and prognosis of scleroderma renal crisis
Must exclude MAHA first
Mainstay of management is prompt BP control - return to baseline BP within 72 hrs
- ACEi first line - captopril. Accept transient rise in creatinine due to relaxation of efferent arteriole and decrease in intraglomerular perfusion pressure (not a reason to cease therapy).
Prognosis
- if untreated, ESRF in 1-2 months and death within 1 year
- with prompt BP control - renal function stabilises or improves in 70%, survival at 1 year is 80%
Risk factors for development of lupus nephritis
Approx. 50% of pts with SLE have renal involvement, lupus nephritis typically occurs within 6 - 36 months of diagnosis. 30% will develop renal impairment, but this is relatively uncommon within the first few years of diagnosis
Risk factors for lupus nephritis
- age <33 yrs at diagnosis
- non-white ethnicity - black, hispanic, asian. More common & more sevre
- male > females
What are the causes of anuric renal failure?
Oliguria - < 400-500ml/day is common in AKI
Anuria - <50-100mL is uncommon in AKI
Causes of anuric renal failure:
1. Shock
2. Complete bilateral urinary tract obstruction
- BPH most common cause in males
- bladder or prostate Ca
- clots
3. HUS
4. Renal cortical necrosis
>50% cases are pregnancy-associated (abruption, infected abortion, eclampsia)
Extreme ATN - significantly diminished perfusion of kidneys due to spasms of feeding arteries, microvascular injury or DIC
3. Bilateral renal arterial obstruction
4. RPGN - especially anti-GBM disease
**diuretics do not prevent AKI or progression to CRRT. Can be used for short term volume control, but should not be used to delay dialysis.
Immunofluorescence in GN
What is the mechanism of hypercoagulability in nephrotic syndrome?
- Loss of anti-thrombin, protein C and S in the urine => increased platelet activation & presence of more fibrinogen in the circulation
- The lower the albumin, the higher the hypercoagulability
- especially in membranous GN
Summary of nephritic syndromes
Causes and clinical associations of IgA nephropathy
- primary mesangial IgA nephropathy is the most common primary glomerular lesion. Most common cause of nephritic syndrome in <40 yrs
- primary IgAN:
Mesangial IgAN
HSP - normally self-limiting, supportive Mx unless significant renal dysfunction or proteinuria
-secondary IgAN
1. Liver cirrhosis - especially ETOH liver disease (associated with failure to clear IgA), also HBV and HCV
2. Celiac disease - about 1/3 pts have IgAN
3. IBD
4. Ankylosing spondylitis
5. Dermatitis herpetiformis
6. Mycosis fungoides
7. HIV infection - however, typically get collapsing FSGS
8. GPA - occurs when in remission after immunosuppressive therapy, pts present with haematuria but no other features of recurrent vasculitis
What is the management of IgA nephropathy?
Treatment of proteinuria
-RAAS blockade (ACEi/ARB) for proteinuria >1g/day, consider for proteinuria 0.5-1g/day, uptitrate to achieve <1g/day proteinuria
Treat hypertension
-if proteinuria >1g/day -> aim BP <125/75mmHg
-if proteinuria <1g/day -> aim BP <130/80mmHg
Role of SGLT2i
-biggest positive trial in IgAN. Start empagliflozin or dapagliflozin if persistent proteinuria >500mg/day despite maximally tolerated doses of ACEi/ARB for at least 3-6 months. Reduces renal progression & risk of death
Immunosuppression
- role of corticosteroids is controversial, may be worth trying in pts with persistent proteinuria > 1g /day despite adequate trial of RAAS blockade
- other immunosuppressive agents (on top of steroids) - increases chances of remission of proteinuria BUT does not slow progression of renal disease
What are the 6 histological classes of lupus nephritis & their key clinical features?
Class I - minimal mesangial LN
Class II - mesangial proliferative LN
Class III - focal membranoproliferative LN
Class IV - diffuse membranoproliferative LN
Class V - membranous LN
Class VI - advanced sclerosing lN
Class I - minimal mesangial LN
- normal light microscopy
- rarely diagnosed because urine typically normal - may have mild proteinuria
- normal renal function
- no therapy, unless progresses to more sinister class
Class II - mesangial proliferative LN
- microscopic haematuria +/- haematuria
- good prognosis; no need to treat unless progresses to more sinister class
Class III - focal membranoproliferative LN
-MOST common & MOST severe
-microscopic haematuria + proteinuria +/- HTN +/- reduced eGFR +/- nephrotic syndrome
-<50% glomeruli involved on light microscopy. Almost always SEGMENTAL involvement of each glom
-needs immunosuppression
Class IV - diffuse membranoproliferative LN
- >50% glomerli involved on light microscopy
- microscopic haematuria + proteinuria + HTN + reduced eGFR + nephrotic syndrome
- low C3, high anti-dsDNA
- segmental OR global involvement of each glomerulus
- needs immunosuppression
Class V - membranous LN
- nephrotic syndrome +/- microscopic haematuria +/- HTN
- normal or slightly elevated creatinine
- may present with no other clinical signs of SLE and normal complement levels
Class VI - advanced sclerosing LN
- slowly progressive renal dysfunction & proteinuria. Usually no haematuria / no active GN.
- global sclerosis > 90% glomeruli - old & scarred
- given no active GN - immunosuppression unlikely to help
Pathophysiology / genetic basis of Alport’s syndrome
- rare genetic disorder
- caused by a mutation in type IV collagen
- type IV collagen is needed for normal function of kidneys, ears, eyes
- three genes which may be involved - COL4 A3, A4, A5
- mutation in COL4 A5 is most common, is X-linked, and has the most severe phenotype
- due to this mutation glycine is replaced by a larger amino acid -> collagen unable to pack tightly
Clinical presentation of Alport’s syndrome
Renal
- haematuria - universal feature of Alport’s syndrome since infancy - can be macroscopic. Milder phenotypes (associated with COL4 A3 and A4 mutations) may just have microscopic haematuria
- proteinuria as renal impairment progresses
Ears
-sensorineural hearing loss, especially loss of hearing at higher frequencies
-hearing typically normal at birth, but develops progressively - usually at stage where renal function is normal but there is proteinuria
Eye - sight not typically affected
- corneal erosions
- lenticonus
- keratoconus
- cataracts
- slit lamp exam - oil droplet reflex ; fundoscopy will show white / yellow flecks on retina
Pathophysiology of ANCA-associated GN
Anti-PR3 and MPO ANCA IgG activate neutrophils
Neutrophils release mediators of acute inflammation
Tissue destruction and cell death
What findings on renal biopsy are suggestive of Alport’s syndrome?
Electron microscopy shows thinning of the basement membrane and basket-weave appearance of the basement membrane
Management of pauci-immune / ANCA-associated GN
Needs immunosuppression
Induce remission
1L steroids or cyclophosphamide
- PO cyclophosphomide is twice the cumulative dose of IV cyclophosphamide. No difference in time to remission, but less ADRs, less leukopenia AND increased risk of renal relapse with IV. No difference between PO and IV in terms of long term mortality and renal function / progression to ESRF.
Plasma exchange for severe cases of ANCA associated renal vasculitis, or if pulmonary haemorrhage, concurrent anti-GBM Abs, severe renal failure
PLEX associated with higher rates of remission
Rituximab is as effective for induction & then maintanence as cyclophosphamide, BUT needs to be ANCA positive for PBS approval.
For maintanence - options are AZA or MMF. AZA is better for ANCA vasculitis (as opposed to lupus nephritis where MMF is better).
Management of Alport’s syndrome
- ACEi in proteinuric patients can slow deterioration of renal function
- most patients rapidly progress to ESRF requiring dialysis in their 20s
- consideration of transplantation (rarely develop Abs to type 4 collagen post transplant, resulting in progressive graft dysfunction secondary to Goodpasture syndrome)
What infections are associated with infection-related GN?
In children (<12) - typically streptococcal URTI or skin infection (mostly URTI)
In adults (>60) - typically staphylococcal infections. Can be skin, bone, heart, teeth, UT, lung, heart). In elderly & diabetic - skin most common source
Outline the principles of management of CKD-MBD
Accept PTH levels 2-4 x upper limit normal - if exceeding this, need to suppress
1. Aim for phosphate level around 2
Calcium based phosphate binders - mainly calcium carbonate
Non-calcium based phosphate binders - sevelamer and lanthanum are only available for patients on dialysis
2. Cholcecalciferol for vitamin D deficiency
3. If PTH does not normalise despite phosphate binders -> consider calcitriol (only if Ca levels are not elevated)
4. For tertiary refractory hyperparathyroidism - consider cinacalcet -> increases sensitivity of calcium sensing receptors. No evidence that cinacalcet decreases cardiovascular mortality
What are the risk factors for developing infection-related GN?
-Male predominance
-Common in children (<12yo) - most common cause of acute nephritis in children
-Immunocompromised - diabetics, elderly, ETOH, AIDs, malnourishment
-TB
-Synthetic valves
-IVDU
-Malignancy
What is the pathophysiology of infection related GN?
Immune complex deposition
Deposition of IgG Abs and C3
Describe the changes to lipid profile in nephrotic syndrome
- hypercholesterolaemia - typically with HDL elevation and hypertriglyceridaemia
- proteinuria => reduced plasma oncotic pressures => increased hepatic lipoprotein synthesis
- hypertrigylceridaemia likely due to impaired metabolism
- can also get lipiduria in nephrotic syndrome
What is the typical clinical presentation of infection-related GN?
Deterioration in renal function - typically weeks after infective precipitant
- up to 95% of children will present with asymptomatic haematuria
- can also present as nephritic syndome
Hypertension 50-90%
Generalised oedema - MOST common symptom - 66% of symptomatic children
Red-brown urine - 30-50%
AKI, acute renal failure and RPGN is rare
What happens to serum complement levels in IgA nephropathy and infection-related GN?
In infection-related GN, serum C3 +/- C4 levels are low in 90% patients
As opposed to IgAN, where complement levels are normal or elevated
What are the findings on renal biopsy that may be suggestive of infection-related GN?
Progressive renal failure is the primary indication for renal bx in suspected infection-related GN
Light microscopy - diffuse proliferative and exudative glomerulonephritis with prominent endocapillary proliferation and numerous neutrophils
IF - diffuse granular pattern of C3 and IgG deposits (compared to IgAN where immune complex deposition is focal and patchy)
What is the management of infection related GN?
Antibiotics if infection still present
Supportive management as prognosis typically excellent
Frusemide 1mg/kg for mx of fluid status
Treat hypertension - nifedipine
Does infection-related GN always progress to ESRF?
No.
Prognosis of infection-related GN is excellent, especially in children. Most children will have normal or modestly reduced renal function up to 18 yrs. post. 20% could have persistently abnormal urinalysis.
Some adults will develop HTN, recurrent proteinuria and renal impairment. This is associated with evidence of glomerulosclerosis on biopsy -> may actually represent membranoproliferative GN rather than infection-related
Association between renal biopsy pattern and prognosis in pauci-immune GN
Sclerotic biopsy pattern is associated with worse prognosis
Definitions of albuminuria
Minimal change nephropathy summary
FSGS summary
Membranous nephropathy summary
What are the differences between primary and secondary FSGS?
- Primary FSGS typically causes diffuse podocyte effacement, secondary FSGS causes segmental effacement
- Primary FSGS typically presents as acute onset nephrotic syndrome - proteinuria (70-100%), haematuria (50%), HTN (20%), AKI (25-50%)
- Secondary FSGS typically presents as slowly progressive proteinuria and renal impairment. Either non-nephrotic proteinuria OR nephrotic range proteinuria without nephrotic syndrome
- Primary FSGS responds well to immunosuppression, whereas focus of Mx in secondary FSGS is underlying cause and supportive management with low protein, low salt diet and BP control
What are the diagnostic features of anti-GBM disease?
Positive anti-GBM IgG serology
Urgent biopsy required if positive serology
Histopath - severe necrotising and crescenteric pattern
IF - strong linear / ribbon-like staining of IgG and C3
Distinguishing pre-renal AKI and ATN
KDIGO CKD stages
What is the mechanism of the renoprotective effects of SGLT2i?
SGLT2i increase tubuloglomerular feedback and increase afferent arteriole tone => decreasing intraglomerular pressure. May initially cause decrease in eGFR, followed by stabilisation. Decrease albuminuria.
Complimentary mechanism to RAAS blockade. ACEi/ARB decrease efferent arteriole tone and decrease intraglomerular pressure.
Causes of EPO resistance
What happens to PTH, Ca, PO4 and Vitamin D in primary, secondary and tertiary hyperparathyroidism
What happens to HbA1c in CKD?
HbA1c is typically falsely LOW in CKD. Due to anaemia / EPO / iron.
