Renal Flashcards
How much HCO3- is filtered by the kidneys daily?
A lot: 4000mM and it is all essentially reabsorbed.
Describe the equation in which carbonic anhydrase relates to HCO3- in the body.
H20 + CO2 — H2CO3 — H+ + HCO-
How is anion gap calculated?
AG = Na+ + K+ - Cl- - HCO3-
With respect to the kidney, how does it handle glucose, inulin and PAH (para-amino hippurate)?
Normal kidneys:
Glucose: completely reabsorbed
Inulin: NOT reabsorbed and NOT secreted
PAH: completely secrete
Inulin - stays IN
PAH - PISSES off
Describe the renal reabsorption of HCO3-
Renal regulation of HCO3-
- Reabsorption in PT (carbonic anhydrase)
- Reabsorption in DT via excretion of H2PO4-
- Reabsorption in DT via excretion of NH4+
What is the histology of membranous glomerulonephritis?
Immune-complexes localised to subepithelial aspect of capillary loop (i.e. between outer aspect of BM and podocyte/epithelium)
True/False: membranous glomerulonephritis is an Ab-mediated disease.
True.
What age-group is membranous glomerulonephritis more likely to occur?
Adults - older than 30yrs.
25% of membranous glomerulonephritis is secondary to another disorder, give 4 common associations.
- SLE and other connective tissue disorders
- Drugs (NSAIDs, gold, penicillamine)
- Infections (Hep B, syphilis, malaria, leprosy, shistosomaiasis)
- Cancer (carcinoma, leukaemia, NHLs)
True/False: membranous glomerulonephritis tends to cause nephritic syndrome.
False.
Membranous glomerulonephritis accounts for up to 50% of adult cases of nephrotic syndrome. Most have insidious heavy proteinuria +/- microscopic haematuria.
Patient is noted to have haematuria, AKI and positive anti-glomerular basement membrane (anti-GBM) antibody on blood test.
Diagnosis?
Treatment?
Goodpasture’s syndrome - autoimmune disease with Abs against type IV collagen.
Prompt treatment required to prevent rapid descent to ESKD.
Treat with plasmapheresis and immunosuppression (prednisone + cyclophosphamide)
In simple terms compare the histopathology of nephrotic and nephritic syndromes.
What is found in the urine?
Nephrotic:
podocyte injury and sclerosis
UA = proteinuria
Nephritic:
glomerular proliferation and inflammation
UA = RBC casts
Give 4 conditions that cause predominantly nephrotic syndrome.
Minimal change nephropathy (MCN) Membranous nephropathy (MN) Focal segmental glomerulosclerosis (FSGS) Diabetic nephropathy (DM)
Give 7 conditions that cause predominantly nephritic syndrome (use mnemomic)
PIG WAIL: Post infectious GN IgA nephropathy Goodpasture's Wegner's Alport Idiotpathic Crescentic GN Lupus Nephritis
Give 3 conditions that cause a ‘mixed’ picture of nephrotic and nephritic syndrome.
- SLE
- Membranoproliferative GN (MPGN)
- IgA nephropathy
What is the normal size of kidneys in the longitudinal direction?
9-12cm
True/False regarding the following comments for urinary pH:
- Urinary pH is affected by diet and vegetarians tend to have acidic urine.
- Bacterial infection are usually associated with acidic urine.
- False: vegetarians have alkaline urinary pH. Animal products have protein that are converted to acidic products that increases body’s acid content.
- False: bacterial infections promote alkaline urine due to bacterial enzymes converting urea to ammonia.
Why are vegetarians more likely to have renal stones?
What types of stones form?
Calcium phosphate stones are more likely to form in alkaline urine with pH > 6.0.
What is the most likely cause of intrinsic AKI?
ATN (acute tubular necrosis)
What is the most common cause of AIN (acute interstitial nephritis)?
How is it diagnosed?
PPIs.
Dx:
- Eosinophilia in blood
- Urine may have eosinophilia and WCC casts
- Low grade proteinuria
What is the clinical significance of FGF-23 in dialysis patients?
Prognostication: high FGF-23 suggest poor eGFR and higher mortality.
What is hepatorenal syndrome?
Renal failure in the setting of severe liver disease, in ABSENCE of other renal pathology.
What is the diagnostic criteria of hepatorenal syndrome (6)?
Renal:
- Cr >133
- Absence improvement in Cr despite 2d of volume expansion and withdrawal of diuretics
- Absence of nephrotoxins
- Absence of shock (impaired renal perfusion)
- Absence of parenchymal kidney disease (normal renal US and no proteinuria/haematuria)
Liver-related:
6. Cirrhosis + ascites
Summary: essentially bad liver and kidney with other causes of renal impairment excluded.
What are the drugs that cause acute interstitial nephritis (AIN)?
What is the non-specific clinical presentation of AIN?
P-NBC:
PPIs
NSAIDs
Beta-lactam antibiotics
Ciprofloxacin
Presentation: fever and rash.
What is the definition of nephrotic syndrome (3-4)?
HA-HOP:
- +/- Hyperlipidaemia
- +/- Accelerated atherosclerosis (arterial or venous clots)
- Hypoalbuminaemia
- Oedema peripherally
- Proteinuria > 3.5g/d
What is the treatment of secondary nephrotic syndrome?
- ACEi/ARB - to lower intraglomerular pressure
- Dietary sodium restriction + loop diuretics - to reduce oedema
- Statin - however lipid derangement often resolve with treatment of disease.
- Anticoagulation if thromboembolic disease occurs (arterial or venous) - heparin then warfarin
What is the treatment approach for primary idiopathic nephrotic syndrome (Membranous, Minimal change, FSGS)?
What are the considerations for Membranous nephropathy?
1st line = Steroids
2nd line = Cytotoxic (CTX) e.g. cyclophosphamide
3rd line = CNIs e.g. cyclosporin A (however this may cause tubulointerstital nephritis)
For Membranous nephropathy:
- Prednisone and CTX for 6m then alternate the 2 agents monthly,
- Warfarinise if Albumin < 20 (risk of spontaneous DVT)
Most common cause of nephrotic syndrome in children?
Most common cause in children = minimal change disease.
What is the most common cause of nephrotic syndrome in non-DM adults?
Most common cause in non-DM adults = membranous.
What biomarker is associated with Membranous nephropathy (MN)?
Is it present in secondary causes of MN?
PLA2R antibody (anti-phospholipase A2 receptor)
Present in 70% of primary/idopathic membranous nephropathy.
NOT present in secondary membranous nephropathy.
What is the lab marker associated with FSGS?
SuPAR is a circulating Urokinase Receptor that is associated with FSGS.
(Flash Gordon (FSGS) is a SuPAR-hero)
What are the secondary causes of Membranous Nephropathy?
HADIC:
Hep B Autoimmune: T1DM, SLE, RA Drugs: ACEi, NSAIDs Infections CLL
What are the biopsy findings of Membranous Nephropathy?
LM/EM:
- Spikes on silver staining
- Electron-dense deposits (due to intramembranous deposits of immunoglobulin)
- Thickened GBM
- Granular deposition
Late disease: interstitial fibrosis and less deposits.
What are the biopsy findings in FSGS?
What part of the nephron is involved first?
LM/EM:
- Sclerosis, focal and segmental (as the name implies)
- Juxtaglomerular nephrons involved first
- Hyalinosis
- Interstitial fibrosis
For type 1 RTA answer the following:
- Site
- Mechanism
- Serum potassium
- Urinary pH and complications
- Severity of acidosis
- Serum HCO3-
- Examples
- Rx
Type 1 RTA (Distal RTA):
- Site: DT
- Mechanism: failure of H+ secretion by alpha-intercalated cells
- Serum potassium: low/normal
- Urinary pH: High (above 5.5) and calcium stones
- Severity of acidosis: severe
- Serum HCO3-: below 15
- Examples (SHADO): stone (nephrocalcinosis), hereditary, autoimmune (Sjogens, SLE, thyroiditis), drugs (amphotericin B), obtructive uropathy
- Rx: treat cause +/- HCO3- replacement
For type 2 RTA answer the following:
- Site
- Mechanism
- Serum potassium
- Urinary pH and complications
- Severity of acidosis
- Serum HCO3-
- Examples
- Rx
Type 2 RTA (Proximal RTA):
- Site: PT
- Mechanism: decreased HCO3- reabsorption
- Serum potassium: low/normal
- Urinary pH: Low (below 5.3) and osteomalacia/rickets
- Severity of acidosis: moderate
- Serum HCO3-: above 15
- Examples (FA): Fanconi’s syndrome and Amyloidosis
- Rx: treat cause + needs HCO3- replacement
For type 4 RTA answer the following:
- Site
- Mechanism
- Serum potassium
- Urinary pH
- Severity of acidosis
- Serum HCO3-
- Examples
- Rx
Type 4 RTA (not really a tubular disorder):
- Site: DT (renal interstitium)
- Mechanism:
a. Defective aldosterone response (Na/K pump defect)
b. No aldosterone - Serum potassium: high
- Urinary pH: low (below 5.3)
- Severity of acidosis: low
- Serum HCO3-: above 15
- Examples:
Defective aldosterone (CN): CKD, NSAIDs
No aldosterone (SAAAD): sickle cell disease, ACEi, ARB, addison’s disease, DM - Rx: treat hyperkalaemia +/- HCO3- (often not required).
Mnemonic for all the GNs?
MISs Pig-Wail gave My Friend DM.
Mixed (MIS): membranoproliferative GN, IgA, SLE
Nephritic (PIG-WAIL): Post-infective GN, IgA nephropathy, Goodpastures, Wegener’s (GPA), Alports, Idiopathic crescentic GN, Lupus
Nephrotic (MFDM): minimal change GN, FSGS, Diabetic nephropathy, membranous GN
NB: IgA and SLE are overlap
