Renal System Flashcards
What type of vasculitis is anti-GBM disease
Small vessel vasculitis. antibodies are produced against Type 4 collagen
2x MC in men
Bimodal age 20-30 yrs & 60-70 yrs
Renal biopsy of Anti-GBM disease
Linear IgG deposits along Basement memb.
Anti-GBM disease Rx.
Plasmapheresis
Steroids
Cyclophosphamide
MCC of Renal vascular disease
Atherosclerosis
Fibromuscular disease (FMD)
Ix & Rx. of Renal vascular disease
IOC - MR Angio
Balloon Angioplasty
Fibromuscular disease (FMD) features
Young Female + HTN + CKD/ ARF (secondary to ACEi initiation) + Flash Pulm. edema
Retroperitoneal Fibrosis C/F
Low back/ Flank pain + Fever & LL edema
Association of Retro P Fibrosis
Riedal’s Thyroiditis
Previous RT
Sarcoidosis
Drug METHYSERGIDE
Rhabdomyolysis biochemical results??
Elevated Cr., CK
Myoglobinuria
Hypocalcaemia (Myoglobin binds to Ca2+)
Elevated K+, PO4-
METABOLIC ACIDOSIS
Rhabdomyolysis Rx.
IV fluids
Urinary Alkalinization
Rhabdomyolysis Causes
Fall at home for long hrs
McArdles syndrome
ECSTACY
Time taken for AV fistula to develop
6 to 8 weeks
Complications of AV fistula
Infection
Thrombosis (ABSENCE of Bruit)
Stenosis
STEAL Syndrome
Plasmapheresis Indications
GBS, Goodpasture’s,
Myasthenia gravis
ANCA +ve Vasculitis
TTP, HUS
Cryoglobulinaemia
Hyperviscosity synd.
Plasmapheresis Complications?
Hypocalcaemia (due to Citrate)
Coagulation factor depletion
IGs depletion
Met. Alkalosis
HLA/ MHC is located on which Chromosome ??
Chr. 6
Class 1 antigen - A, B, C
Class 2 antigen - DP, DQ, DR
Renal transplant imp. HLA
DR»>B»>A
Graft survival of type of donor??
Living donor»>Cadaveric donor
Hyperacute Graft Rejection type of HS reaction???
1) Hyperacute - Minutes to Hrs.,
Type 2 HS reaction
Caused by Pre-existing antibodies against ABO or HLA antigens.
Rx. Remove the graft
Type of Graft Rejection
1) Hyperacute (min to hrs)
2) Acute (< 6 months)
3) Chronic (> 6 months)
Acute Graft rejection is due to??
Mismatched HLA. CMI (cytotoxic T cells)
MONOCLONAL cell infiltrate predominates
CMV infection
Rx. Steroids & Immunosuppresants
Chronic Graft Rejection is due to ??
Both Antibody + CMI mechanisms
results in Fibrosis of transplanted kidney (CHRONIC ALLOGRAFT Nephropathy)
Rx. for Renal transplant??
Immunosuppression
1) Initial = Ciclosporin/ Tacrolimus + a Monoclonal antibody
2) Maintenance = Ciclosporin/ Tacrolimus + MpMF or Sirolimus
add Steroid if >= 1 steroid responsive acute rejection
Recurrence of original renal disease in Transplanted Kidney ???
MCGN»IgA»FSGS
LUTS voiding features??
Hesitancy
Poor/ Intermittent stream
Straining
Incomplete emptying
Terminal dribbling
LUTS Storage C/F ??
Urgency
Frequency
Nocturia
U Incontinence
LUTS post-micturition C/F ??
Post M dribbling
Sensation of incomplete emptying
Rx. if predominantly voiding C/F???
-Conservative = Pelvic floor exercise, Bladder training, prudent Fluid intake
-Moderate - severe symp. = ALPHA Blockers
- Prostatomegaly + high risk of progression = 5 alpha reductase inhibitors
- Prostatomegaly + moderate to severe symp. = Alpha blockers + 5 alpha reductase
Mixed Voiding & Storage symp. Rx. ??
Alpha blockers {If does not respond, Anti-Muscuranic (Anti-cholinergic) eg. tolterodine or darifenacin is added}
Predominantly Overactive bladder Rx. ??
-Fluid intake moderation
-Bladder retraining
-Anti-Muscarinic drugs (Oxybutinin, Tolterodine are immediate release & Darifenacin is once daily prep.)
- Mirabegron [if 1st line drugs fail]
Nocturia Rx. ??
-Moderate Fluid intake at night
- Furosemide 40mg in late afternoon
- Desmopressin
Types of Haematuria??
Non-Visible (Microscopic or Dip-stick +ve)
Visible (macroscopic)
Red or Orange Urine discolouration causes???
Beetroot, Rhubarb
Doxorubicin, Rifampicin
IOC for Haematuria??
Urine dipstick
Renal colic analgesia of choice??
NSAIDs (Diclofenac)
inpatients = Parenteral Diclofenac (IM)
What is Persistent Non-Visible Haematuria??
+ve blood in 2 of 3 samples tested 2-3 wks apart
What is the Surgical emergency in renal stones??
Ureteric obstruction (due to stones) + Infection
Renals must be decompressed
Imaging in Renal Calculi??
-NCCT-KUB (in < 14hrs of admission)
- If Fever/ solitary kidney/ Dx. uncertain (to exclude ruptured AAA)== Immediate CT-KUB
Oxalate stones prophylaxis??
- CHOLESTYRAMINE (reduces urine oxalate excretion)
- PYRIDOXINE (reduces urine oxalate secretion)
Radio-Lucent stones??
- Urate stones
- Xanthine stones
Urate stones prophylaxis??
Allopurinol
Urinary Alkalinization (Oral HCO3-)
Ca2+ stones prophylaxis??
- High fluid intake
- Low salt (NOT low Ca2+ diet)
- Low animal protein diet
- Thiazides (increases DCT Ca2+ resorption)
Semi-opaque or Ground glass appearance of stone cause??
Cysteine stones
MC type of renal stone??
Ca. OXALATE (40%)>Mixed Ca Oxalate/ Phosphate sones (25%)»_space; Triple Phosphate stones (10%) = Ca Phosphate (10%)»_space; Urate stones (5- 10%)»_space; Cysteine stones (1%)»_space; Xanthine (<1%)
Risk Factor for Urate stones??
- Gout
- ILEOSTOMY (loss of HCO3- & fluids results in Acidic urine, causes ppt. of uric acid)
Drugs causing Ca2+ stones??
- Loop diuretics
- Steroids
- Acetazolamide
- Theophylline
Stag-horn calculi features??
- Made of Struvite (Mg, NH4, PO4)
- aka Triple phosphate or Infection stones
- Renal pelvis + involves <= 2 calyces
- develops in Alkaline urine
- Common in UTIs
Rx. of Epididymo-orchitis ??
- Unknown organism = Ceftriaxone 500mg IM single dose + Doxycycline 100mg oral 1-0-1 for 10 to 14 days
MCC of Epididymo-orchitis??
- Local spread of infection from genital tract (C trachomatis, N gonorrhoea - STIs)
- from Bladder (E coli typically seen in elderly & in low risk sexual history)
Organisms predisposing to Stag-horn calculi???
Ureaplasma urealyticum infection
Proteus infection
Testicular torsion features??
< 20yrs + severe pain + acute onset
Ix. for Epididymo-orchitis??
- Young = look for STIs
- Elderly + low risk sexual Hx. = MSU for microscopy & culture
BPH ethnicity variance ??
Black > White > Asians
Ix for suspected chronic retention in BPH ???
U & E
Indication for PSA testing ??
- Obstructive symp.
- Pt. is worried about Prostate Ca
Rx. if Prostatomegaly (significant) + high risk of progression ??
5 alpha reductase inhibitors (Finasteride)
Rx. if IPSS >= 8 (moderate to severe voiding symp.) ??
Alpha-1 antagonists (Tamsulosin, Alfuzosin)
International Prostate Symp. Score (IPSS) ??
Tools used = Severity of LUTS & Impact of LUTS on quality of life
- 0 to 7 = Mildly symptomatic
- 8 to 19 = Moderately
- 20 to 35 = Severely
When is a combination of Alpha 1 antagonist + 5 alpha reductase inhibitor used ??
Moderate to severe voiding symp. + Prostatomegaly
Chemotherapy DoC in Prostate Ca ??
Docetaxel
When is an Androgen syn. inhibitor (eg. ABIRATERONE) used in prostate Ca. ??
- Hormone relapsed metastatic prostate Ca. +
- have no/ mild symp. after androgen deprivation therapy has failed +
- Before Chemo is indicated
eg.- ABIRATERONE
Rx. for Localized Prostate Ca (T1/ T2)??
- Conservative (active monitoring + watchful wait)
- Radical prostatectomy
- RT (Ext. beam & Brachytherapy)
Rx. for Localized advanced prostate ca. ??
- Hormone therapy
- Radical Prostatectomy ( erectile dysfunc. is common complication)
- RT (Ext. beam + Brachytherapy)
IoC to look for Renal scarring ??
DMSA
Steroidal anti androgen MoA ??
- Prevents DHT binding from Intracytoplasmic protein complex
- eg.- CYPROTERONE ACETATE
What do you suspect in
- Antenatal USS shows Hydronephrosis
- Recurrent UTI in childhood
- Chr. Pyelonephritis in children MCC
Vesico- Ureteric Reflux
{Renal scarring can cause increased quantity of RENIN ==> HTN}
Why do we use Low dose, long term GnRH agonists (Zoladex) for hormonal therapy in Prostate Ca. ??
Low LH levels for long term ==> OVERSTIMULATION ==> disruption of Endogenous hormonal Feedback systems.
The testosterone levels initially rise (Tumour Flare) before falling to castration levels
Non Steroidal anti-androgen MoA ??
- Blocks Androgen receptor
- eg.- BICALUTAMIDE
RF for Urothelial (Transitional cell) CA ??
- Smoking (Hazard ratio is 4)
- Aniline dyes (Printing & Textile industries) 2-Naphthylamine & Benzidine
- Rubber manufacture
- CYCLOPHOSPHAMIDE
Hormonal therapy for Prostate Ca. ??
Low dose, long term GnRH agonists (Zoladex) + Anti- androgen (initially to prevent Tumour flare)
Triad of RCC ??
Haematuria
Loin pain
Abdominal mass
IoC in VUR ??
Micturating Cystourethrogram
RF for Squamous Cell CA of Bladder ??
‘SSS’
- Schistosomiasis
- Smoking
Grades of VUR ??
G1 - Reflux into ureter only + NO dilatation
G2 - Reflux into Renal pelvis on micturition + NO DILATATION
G3 - Mild/ Moderate dilatation of Ureter, Renal pelvis, Calyces
G4 - Dilatation of Renal pelvis & Calyces + Moderate ureteral TORTUOSITY
G5 - Gross dilatation of URETER, pelvis and calyces + ureteral Tortuosity
Site of RCC origin ??
Proximal Renal Tubular Epithelium
- Clear cell CA (MC histological subtype)
What is Stauffer synd.??
- Paraneoplastic disorder a/w RCC
- presents as Cholestasis/ Hepatosplenomegaly
- Thought to be secondary to INCREASED levels of IL-6
Endocrine effects of RCC ??
May secrete-
- Erythropoietin (Polycythaemia)
- Parathyroid Hormone-related protein (Hypercalcaemia)
- Renin
- ACTH
What sided varicocele does RCC cause ??
- Majority are LEFT sided (due to compression by tumour)
RCC T categories of tumour ??
T1 : <= 7cm + confined to kidney
T2 : > 7cm + confined to kidney
T3 : Tumour extends to major veins or Perinephric tissue + but NOT into I/L Adrenals & NOT beyond Gerota’s fascia
T4 : Invades beyond Gerota’s fascia + extension into I/L Adrenals
Rx. of RCC ??
T1 tumour : Partial Nephrectomy
Reduce tumour size : Alpha-IFN & IL-2
{Note- Receptor TK inhibitors (Sorafenib, Sunitinib) are superiorly efficacious than Alpha-IFN}
Tumour Markers of testicular ca. ??
Germ cell tumour
- Seminoma : hCG (elevated in 20%)
- Non seminomas : AFP &/or Beta-hCG (elevated in 80%-85%)
LDH is increased in 40% 0f Germ cell tumour
Types of Testicular Ca. ??
Germ Cell tumors (95% of Ca.)
- Seminomas
- Non seminomas : includes embryonal, yolk sac, Teratoma & ChorioCA
Non-Germ cell tumours
- Leydig cell tumour
- Sarcomas
MCC of scrotal swelling seen in primary care ??
Epididymal cysts (MC found posterior to Testicles)
Why do we see Gynaecomastia in Testicular Ca ???
Due to increased Oestrogen : Androgen ratio
- Germ cell tumour {hCG => Leydig cell dysfunc. => Increase in both O & T production (but O rise»_space; T rise)}
- Leydig cell tumour {O secretion more + converts additional androgen precursors to O}
Features of Wilm’s tumour ??
ABDOMINAL Mass (MC presenting feature)
- Painless Haematuria
- Flank pain
- Anorexia, Fever
- U/L in 95% cases
Metastases in 20% cases (MC site is LUNG)
What is Hydrocele ??
Accumulation of fluid within TUNICA VAGINALIS
MC type of Hydrocele in Newborn Males ??
Communicating type (Peritoneal fluid drains down to scrotum via PROCESSUS VAGINALIS)
Which Testicular swelling occurs
- Posterior to testes
- Anterior to testes
- Epididymal cyst
- Hydrocele (anterior & down)
What are the requirements for Maintenance fluids ??
25 to 30ml/kg/day of Water
Approx. 1mmol/kg/day of K+, Na & Cl
Approx. 50 to 100g/day of Glucose to limit Starvation ketosis
MC site of Varicocele ??
LEFT side (> 80%)
Bag of worms
Subfertility is common
0.9% NaCl in large volumes increase the risk of ??
Hyperchloraemic Met. Acidosis
Anion gap formulae ??
{(Na+) + (K+)} - {(HCO3-) + (Cl-)}
Normal Anion gap is 8 to 12 mEq/L
CI for Hartmann’s ??
Hyperkalaemia
Causes of increased Anion gap (>12 mEq/L) M acdosis ??
GOLDMARK:
- Glycols (Ethylene g & Propylene g)
- 5-Oxoproline (Chr. Acetaminophen use)
- Lactic acidosis
- Exogenous Lactic acid
- Methanol (& other alcohols)
- Aspirin (Late effect)
- Renal failure (Urate)
- Ketosis (Diabetic, Alcoholic, Starvation)
Causes of Normal Anion gap M acidosis ??
SHARDS FU
- Spironolactone
- Hyperchloremia/ Hyperalimentation
- Addison’s/ Acetazolamide use/ Ammonium Cl injection
- Renal Tubular Acidosis
- Diarrhoea
- Saline Infusion
- Fistula
- Uterosigmoidoscopy
Types of Lactic Acidosis ??
Type A : Sepsis, shock, hypoxia, burns
Type B : METFORMIN
Salycylates poisoning ABG changes??
Early- Resp. Alkalosis
Late- Met. Acidosis
Drugs causing Hyperkalaemia ??
K+ sparing diuretics
ACEi & ARBs
Ciclosporin, Heparin (UnF & LMW)
Beta-blockers in renal failure pts.
How does LMWH & UnFH causes Hyperkalaemia ??
by Inhibition of Aldosterone secretion
Hyperkalaemia classification ??
Mild = 5.5 to 5.9 mmol/L
Moderate = 6.0 to 6.4 mmol/L
Severe : >= 6.5 mmol/L
Sequential ECG changes in Hyperkalaemia ??
Peaked T waves (occurs 1st)
Loss of P wave
Broad QRS complex
Sinusoidal wave pattern
Asystole
What is Pseudo-Hyperkalaemia ??
Elevated K+ levels due to
- Excess leak of K+ from cells during or after the blood is taken
Lab. modification to prevent Pseude-Hyperkalaemia ??
- use Lithium heparin tube
- request Slow spin in centrifuge
- do not apply excessive vacuum while drawing blood (causes haemolysis)
Gynaecomastia is less commonly seen with which K+ sparing diuretics ??
Eplerenone
Indication of Spiranolactone in HF (RALES) ??
NYHA 3 + 4 & pt. already on ACEi
Low dose Spironolactone reduces ALL CAUSE MORTALITY
Indications of Spironolactone ??
- Ascites (Cirrhosis pts. develop Secondary Hyperaldosterone); large doses 100/200mg are used
- HTN: Step 4 Rx.
- Nephrotic
- Conn’s
Hypokalaemia ECG changes ??
ST depression
Flat T wave
U wave
QT interval prolongation
Causes of Hypokalaemia with Alkalosis ??
Vomiting (H+ loss)
Thiazides & Loop diuretics
Cushing’s synd.
Conn’s synd. (primary hyperaldosteronism)
Causes of Hypokalaemia with Acidosis ??
Diarrhoea (HCO3- loss)
Renal Tubular Acidosis
Acetazolamide
Partially treated DKA
Fanconi’s synd.
Causes of Hypokalaemia with HTN ???
Cushing’s synd.
Conn’s synd.
Liddle’s synd. (disordered Na+ channel in DCT)
11-beta Hydroxylase deficiency
Anti-ulcer drug (CARBENOXOLONE)
Liquorice excess
Causes of Hypokalaemia without HTN
Diuretica
GI loss (diarrhoea & vomiting)
Barter’ synd.
Gitelman synd.
RTA (type 1 & 2)
What is “Fanconi’s BaGeLS” ??
Fanconi’s : PCT defect
Bartter’s : Thick Ascending loop of henle (affects Na+/K+/2Cl- triple transporter)
Gitelman’s : NaCl transporter reabsorption defect in DCT
Liddle’s : Gain in func. mutation (decreased Na+ channel degradation) –> increased Na+ reabsorption from Collecting duct
SAME : Synd. of Apparent Minerelocorticoid Excess (Heriditary 11-Beta HSD deficiency ==> increase Cortisol ==> increase MC receptor activity)
AKI Dx. criteria ??
- Rise in S. Cr by >= 26 umol/L in 48hrs (OR)
- a >= 50% rise in S. Cr within past 7 days (OR)
- UO < 0.5 ml/kg/hr for >= 6hrs in adults & >= 8hrs in children (OR)
- > = 25% fall in eGFR in children/ young adults in 7 days
What is Thin Basement Memb. disease ??
Inherited Type 4 collagen defect (thinning of BM)
Persistent Haematuria + normal KFT without renal failure + Familial haematuria.
Acute Interstitial Nephritis features ??
Fever + Rash + Arthralgia
EOSINIPHILIA
Mild renal impairment + HTN
U/R - Sterile pyuria & WBC casts
Drugs causing AIN ??
Penicillin
Rifampicin
NSAIDs
Allopurinol
Furosemide
AIN histology ??
marked Interstitial edema & infiltrates in connective tissue b/w renal tubules.
Types of Glomerulonephritis ??
NEPHROTIC (Proteinuria, oedema)
-Minimal Change disease
- Membranous GN
- FSGS
- Amyloidosis
- Diabetic Nephropathy
NEPHRITIC (Haematuria, HTN)
- RPGN or Cresentric GN
- IgA Nephropathy or Mesangio-proliferative GN)
- Alport Synd.
MIXED (Nephrotic + Nephritic)
- Diffuse Proliferative GN
- Membrano-proliferative GN or Mesangio-capillary GN
- Post- Streptococcal GN
Disorders a/w GN & Low Complement ??
PSGN
SABE
SLE
Mesangio-capillary GN or Memb.-Proliferative GN
What is FSGS ??
Is a cause of Nephrotic synd. & Chr. Kidney disease
- YOUNG adults
Causes of FSGS ??
Idiopathic
Secondary to Renal pathology
- IgA Nephropathy
- Reflux Nephropathy
HIV
Heroin
Alport’s & Sickle Cell D
High recurrence rate in Renal transplants
Renal Biopsy features of FSGS ??
Light Microscopy: Focal & Segmental Sclerosis & Hyalinosis
Electron M: Foot process effacement
Rx.
- Steroids +/- Immunosuppresants
What is HIVAN ??
HIV associated Nephropathy
- May occur as a consequence of Rx. or the Virus itself
Key Features are
- Massive Proteinuria
- Normal or Large Kidney
- FSGS + Focal or Global Capillary collapse
- Elevated Urea & Cr
- Normotension
ART improves the outcome
Difference b/w IgA Nephropathy & PSGN ??
IgA Nephropathy (Nephritic)
- Develops 1- 2 days after URTI
- Young males + Macroscopic Haematuria
PSGN (Mixed Nephropthy)
- Develops 1- 2 wks after URTI
- Proteinuria>Haematuria
- LOW Complement
PSGN cause ??
Grp. A Beta haemolytic Streptococci infection (Strept. pyogenes)
- Caused by Immune Complex (IgG, IgM & C3) deposition in glomeruli
- MC among Young Children
Features
- Proteinuria>Visible Haematuria
- Oedema, Oliguria, HTN
- Low C3 & Raised ASO titres
Renal Biopsy features of PSGN ??
Causes Acute, Diffuse P GN
Endothelial proliferation with Neutrophils
Electron M: SubEpithelial Humps due to lumpy immune complex deposition
Immunoflorescence: Granular or ‘Starry Sky’ appearance
What is HSP ??
Henoch-Schonlein Purpura
- IgA mediated Small vessel vasculitis
- MC seen in Children after infection
- Excellent prognosis without Renal involvement (in Children)
Features of HSP ??
- Palpable purpuric rash (with localized edema) over Buttocks & Extensor surfaces of arms & legs
- Abd. Pain
- Polyarthritis
- Features of IgA nephropathy can occur (Haematuria, Renal failure)
Rx. of HSP ??
- Analgesia for pain
- Rx of Nephropathy is SUPPORTIVE
What is HUS ??
Generally seen in Young Children
Secondary HUS- Typical (most cases)
- Shiga Toxin-Producing E Coli O157:H7 (Verotoxigenic, Enterohaemorrhagic) MCC in children in >90%
- Pneumococcal infection
- HIV
- Rare: SLE, drugs, cancer
Primary HUS- Atypical due to Complement dysregulation
Features & Ix. done in HUS ??
AKI + MAHA + Thrombocytopaenia
FBC: Anaemia, thrombocytopaenia, fragmented blood films
U&E: AKI
Stool culture
- Look for STEC O157:H7 infection
- PCR for Shiga toxins
Rx. of HUS ??
SUPPORTIVE
- Fluids, Blood T, Dialysis (if required)
NO role of Antibiotics
- Plasma exchange
- Eculizumab (a C5 inhibitor monoclonal antibody) has greater efficacy than Plasma exchange in Rx. of Adult HUS
Indication of Plasma exchange in HUS ??
Severe HUS + NOT a/w Diarrhoea
What is Membranoproliferative GN ??
aka Mesangio-capillary GN: presents as Nephrotic, Haematuria/Proteinuria
Type 1 (90% cases)
- Cause: Cryoglobulinaemia, Hep.C
Type 2 (Dense deposit disease)
- Cause: Partial Lipodystrophy (loss of SubC tissue from face), Factor H deficiency
Type 3 :- Causes: Hep. B & C
Rx.- Steroids may be effective
Type 1 & Type 2 Electron microscopy features ??
Type 1: Subendothelium & Mesangium immune deposits of electron-dense material resulting in ‘Tram-Track’ appearance
Type 2: Intramembranous Immune Complex deposits with ‘Dense deposits’
Features of Type 2 Memb.-Proliferative GN ??
Due to Persistent activation of Alternative Complement pathway
- Low circulating C3
C3b nephritic factor found in 70%
- Antibody to Alternative-pathway C3 convertase (C3bBb)
- Stabilizes C3 convertase
What is Membranous GN ??
MC type of GN in adults & is the 3rd MCC of ESRF; Nephrotic picture
Causes
- Idiopathic (Anti-phospholipase A2 antibodies)
- Infections: Hep.B, Malaria, Syphilis
- Malignancy: Prostate, Lung, Lymphoma, Leukaemia
- Drugs: Gold, Penicillamine, NSAIDs
- SLE (Class V), Thyroiditis, RA
Renal biopsy features of Memb. GN ??
Electron M: BM is thickened with Sub-epithelial electron dense deposits
- This creates ‘Spike & Dome’ appearance
Rx. of Memb. GN ??
All pts.- ACEi or ARBs
Immunosuppresion
- Only Severe or Progressive cases
- Steroids alone are not effective; use a combination of Corticosteroids + another agent like (Cyclophosphamide)
Anti-Coagulation in high risk pts.
Good prognostic factors of Memb. GN ??
- Female sex
- Young age at presentation
- Asymptomatic proteinuria of modest degree at the time of presentation
What is Minimal Change disease ??
NEPHROTIC picture (75% are Children & 25% are Adults)
Causes
- Drugs: NSAIDs, Rifampicin
- Hodgkin’s lymphoma, Thymoma
- INFECTIOUS MONONUCLEOSIS
Pathophysiology of Minimal Change disease ??
T-cell & Cytokine mediated damage of GBM => Polyanion loss => reduced Electrostatic charge => Increased permeability of GBM (Highly selective Proteinuria)
Features of MCD ??
Nephrotic syndrome + Normotensive
Only Intermediate-sized proteins such as ALBUMIN & TRANSFERRIN leak through GBM
Rx.-
- Oral Corticosteroids (80% are steroid responsive)
- Cyclophosphamide: if Steroid resistant case
Renal Biopsy features of MCD ??
Light M: Normal glomeruli
Electron M: Fusion of podocytes & Foot processes effacement
What is RPGN ??
Rapid loss of renal function a/w the formation of Epithelial Crescents in the majority of glomeruli
Causes-
- Goodpasture’s syndrome
- Wegener’s granulomatosis
- SLE, Microscopic Polyarteritis
Features of Crescentric GN ??
RPGN
- Nephritic: Haematuria with Red cell casts, proteinuria, oliguria
- Features of the underlying cause
MC form of Renal disease in SLE ??
Diffuse Proliferative G N
What is Calciphylaxis ??
Complication of End-stage Renal F
- Results in deposition of Ca2+ within the arterioles => Microvascular occlusion & Necrosis of supplied tissue
- PAINFUL, Necrotic skin lesions
RF and Rx. of Calciphylaxis ??
- Hyper Ca2+, Hyper PO4, Hyperparathyroidism
- Warfarin
Rx.- - Reducing Ca2+ & PO4 levels
- Controlling Hyperparathyroidism
- Avoid contributory drugs
When does EPO therapy fails ??
Iron deficiency anaemia
Inadequate dose
Concurrent infection/ Inflammation
Hyperparathyroid Bone disease
Aluminium toxicity
Major S/E of EPO ??
- Pure Red cell Aplasia (due to anti-bodies against EPO)
DARBEPOIETIN has reduced risk - Iron deficiency secondary to Increased Erythropoiesis
Which factors are lost in Nephrotic syndrome ??
- Anti-Thrombin 3, Protein C & S + Rise in Fibrinogen levels (predispose to Thrombosis)
- Thyroxine-binding Globulin is lost ==> Lowers TOTAL but not Free Thyroxine levels
Complications of Nephrotic Synd. ??
Thromboembolism (Loss of Anti-thrombin 3 & Plasminogen in urine)
- DVT, PE
- Renal Vein T => Sudden deterioration in RFT
HYPERLIPIDAEMIA (increased risk of ACS & Stroke)
Increased risk of infection (IGs loss via urine)
HYPOCALCAEMIA (Vit D & Binding protein lost in urine)
Triad of Nephrotic Synd. ??
What is Contrast Media induced Nephrotoxicity ??
25% increase in Cr occurring in < 3 days of IV Contrast media administration
Risk Factors
- Known Renal impairment
- Age > 70 yrs
- Dehydration
- Cardiac failure
- Use of Nephrotoxic drugs (NSAIDs)
How to prevent Contrast induced Nephrotoxicity ??
- IV 0.9% NaCl at 1ml/kg/hr for 12 hrs Pre- & Post procedure
- High-risk pts.- STOP Metformin for 48hrs & until U&E is shown to be normal
What is Renal Papillary Necrosis ??
COAGULATIVE Necrosis of Renal Papillae
Causes
- Severe Acute Pyelonephritis
- Diabetic Nephropathy
- Obstructive Nephropathy
- Analgesic Nephropathy (Phenacitin, NSAIDs)
- TB. - Sickle Cell Anaemia
Features of Renal Papillary Necrosis ??
Fever + Haematuria & Proteinuria + Loin pain
IVU: Papillary Necrosis with Renal Scarring- ‘Cup & Spill’
Common causes of Polyuria ??
Common (> 1 in 10)
- Diuretics, Caffeine, Alcohol, Lithium
- DM, Heart Failure
Infrequent (1 in 100)
- Hyper Ca2+ & Hyperthyroidism
Rare (1 in 1000)
- Chr. Renal Failure
- Primary Polydipsia ; HYPO K+
Very Rare (<1 in 10,000)
- Diabetes insipidus
What is Diabetes Insipidus ??
Cranial DI: Decreased ADH secretion from Pituitary
Nephrogenic DI: ADH insensitivity
Features
- Polyuria
- Polydipsia
Causes of Cranial & Nephrogenic DI ??
CRANIAl DI
- Idiopathic, Post Head injury, Pituitary Sx., [DI DM OA D- Wolfram]
- Infiltrative (Histiocytosis X & Sarcoidosis)
NEPHROGENIC DI
- Genetic (MC form): Aquaporin 2 ADH channel mutation
- Hyper Ca2+ & Hypo K+
- Lithium & Democlocycline
-Tubulo-interstitial disease: Obstruction, Sickle-CD, Pyelonephritis
Ix. & Rx. of Diabetes Insipidus ??
- HIGH Plasma & LOW Urine Osml
- Urine Osml of > 700mOsm/kg excludes DI
- Water Deprivation Test
Rx. - NDI: Thiazides, Low salt/ Protein diet
- CDI: Desmopressin
What are the stages of Diabetic Nephropathy ??
1 : Hyperfiltration- GFR increased (may be reversible
2 : Silent/ Latent- GFR remains elevated + No Microalbuminuria for 10 years
3 : Incipient- Microalbuminuria ( 30 - 300 mg/day) + Dipstick (-)ve
4 : Overt- Persistent proteinuria (>300 mg/day) + Dipstick (+)ve; HTN present + Diffuse GS & Focal GS (Kimmelstiel-Wilson Nodules)
5 : ESRD + GFR < 10 ml/min ; Renal Replacement therapy needed
WHO classification of Lupus Nephritis ??
Class 1: Normal Kidney
C 2 : Mesangial GN
C 3 : Focal Segmental Proliferative GN
C 4 : DIFFUSE PROLIFERATIVE GN
C 5 : Diffuse Membrabous GN
C 6 : Sclerosing GN
What is Class 4 Lupus Nephritis ??
Diffuse Proliferative GN (MC & Most SEVERE form)
- Glomeruli: Endothelial & Mesangial proliferation, ‘Wire-Loop’ appearance
- Capillary wall thickened (immune complex deposition)
- Electron M: Sub-Endothelial Immune Complex deposits
- Immunofluorescence: Granular
Rx. of Lupus Nephritis ??
Treat HTN
Class 3 (Focal) or Class 4 (Diffuse)
- Glucocorticoids + Mycophenolate/ Cyclophosphamide
MMF preferred over Azathioprine
What is Fanconi’s Syndrome ??
Generalised reabsorptive disorder of renal tubule transport in PCT resulting in
- Type 2 RTA (Proximal)
- Polyuria
- Aminoaciduria
- Glycosuria, Phosphaturia
- Osteomalacia
Causes & MCC in Children of Fanconi’s synd. ??
Sjogren’s syndrome
Multiple Myeloma
Nephrotic Synd.
Wilson’s disease
MCC in Children: CYSTINOSIS
What is Alport’s Syndrome ??
- 85% cases: X-linked D & rest as A R
- Type 4 Collagen defect => Abnormal GBM
- More severe in MALES
Features of Alport’s syndrome ??
Usually presents in Childhood
- Microscopic Haemturia
- Progressive Renal Failure
- B/L SNHL ; - Retinitis Pigmentosa
- Lenticonus: Lens surface protrusion to Anterior chamber
Dx. of Alport’s syndrome ??
Molecular Genetic testing
Renal Biopsy
- Electron M: Longitudinal SPLITTING of Lamina densa of GBM resulting in ‘Basket weave’ appearance
Typical Alport’s syndrome presentation ??
Failing renal transplant (may be caused by the presence of Anti-GBM antibodies leading to Goodpasture’s syndrome like picture)
What is Amyloidosis ??
Extracellular deposition of an Insoluble Fibrillar protein termed Amyloid [Fibrillary + Non-fibrillary components]
- Non-fibrillary component: Amyloid-P, Apolipoprotein-E & Heparan sulfate proteoglycan
Types of Amyloidosis ??
AL amyloidosis (MC form)
- L is IG light chain fragment
- Due to Myeloma, Waldenstrom’s, MGUS
- Features: Nephrotic, CVS & CNS involved, Macroglossia, Periorbital eccymoses
AA amyloidosis
- A: precursor serum amyloid A protein, an acute phase reactant
- Seen in Chronic infection/inflam.
- eg.- TB, Bronchiectasis, RA
- Features: Renal involvement MC
Beta-2 Microglobulin amyloidosis
- Beta-2 microglobulin is the precursor protein (part of MHC)
Which type of amyloidosis is a/w
- Pts. on Renal dialysis ??
- TB, Bronchiectasis, RA ??
- Myeloma, Waldenstrom’s, MGUS ??
- Beta-2 microglobulin amyloidosis
- AA amyloidosis
- AL amyloidosis
Dx. of Amyloidosis ??
Congo-red staining: Apple-green birefringence
Serum Amyloid precursor scan
Biopsy: Skin, Rectal mucosa or Abd. fat
Which is the most common inherited cause of Kidney disease ??
ADPKD (1 in 1000 Caucasians)
2 types
- Type 1 (85% cases); Chr 16; presents with early Renal failure
- Type 2 (15% cases) Chr. 4
2 disease loci have been identified, PKD1 & PKD2, which codes for Polycystin-1 & Polycystin-2 respectively
Ix. done in ADPKD ??
Screening Ix for relatives is USS abd.
USS Dx. criteria in pts. with (+)ve FHx
- 2 cysts, U/L or B/L if aged < 30yrs
- 2 cysts in B/L Kidneys; aged 30 to 59 yrs
- 4 cysts in B/L Kidneys; aged > 60yrs
Rx. of ADPKD ??
TOLVAPTAN (vasopressin receptor 2 antagonist) in adults to slow the progression of cyst devt. & renal insufficiency ONLY if:
- CKD stage 2 or 3 at the start of Rx
- Evidence of Rapid Progressive disease
- The company provides it with discount agreed in pt.’s scheme
What are the Renal & Extra-renal features of ADPKD ??
- HTN, Recurrent UTIs, Haematuria
- Renal Stones, Abd. Pain, CKD
Extra-Renal manifestations - Liver cysts: can cause Hepatomegaly
- BERRY Aneurysm: causes SAH
- CVS: MVP, Mitral/ Tricuspid incompetence, Aortic Root dilation, Aortic dissection
- Cysts in other organs: Pancreas, Spleen; very rarely- Thyroid, Oesophagus, Ovary
MC Extra-renal manifestation of ADPKD ??
Liver Cysts
Features of ARPKD ??
Gene defect located on Chr. 6 which encodes for FIBROCYSTIN- protein imp. for normal renal tubule devt.
Dx.
- Prenatal USS or Early Infancy with Abd. mass & Renal failure
- Newborns: Potter’s syndrome secondary to Oligohydramnios
- ESRD in childhood
-Liver: Portal or Interlobular fibrosis
Renal Biopsy
Renal Biopsy features of ARPKD ??
Multiple Cylindrical lesions at Rt. angles to Cortical Surface.
Causes of AKI ??
PRE-RENAL (Ischaemia or Lack of Blood flow to Kidneys)
- Hypovolaemia (diarrhoea/vomitting)
- Renal artery Stenosis
INTRINSIC Renal
- Glomerulonephritis
- ATN. - AIN. - Rhabdomyolysis
- Tumour Lysis Syndrome
POSR-RENAL (Obstruction)
- Renal stones in Ureter/ Bladder
- BPH. - External Ureter compression
C/F of AKI ??
Early AKI can be asymptomatic
- Reduced Urine Output
- Pulm. or Peripheral Oedema
- Arrhythmias (due to changes in K+ & Acid-base balance)
- Uraemia features (eg.- Pericarditis or Encephalopathy)
Dx. of AKI ??
(p)RIFLE, AKIN or KDIGO criterias
- Rise in Cr. of >= 26 umol/L in < 48hrs
- Rise in Cr >= 50% known/ presumed to have occurred in past 7 days
- Fall in UO to < 0.5ml/kg/hr for >6 hrs in Adults & > 8hrs in Children
- Fall of >= 25% in eGFR in Children/ Young adults in 7 days
URINALYSIS
IMAGING
- No identifiable cause or at risk of Urine tract obstruction; Renal USS within 24hrs
KIDGO staging of AKI ??
STAGE 1
- Rise in Cr. to 1.5- 1.9 times baseline/
- Rise in Cr. by >= 26.5 umol/l or
- Fall in UO < 0.5ml/kg/hr for >=6hrs
STAGE 2
- Rise in Cr. to 2.0 to 2.9x baseline
- Fall in UO < 0.5ml/kg/hr for >=12hrs
STAGE 3
- Rise in Cr. to >= 3.0x baseline or
- Rise in Cr. of >= 353.6 umol/l or
- Fall in UO <=0.3ml/kg/hr for >=24hrs
- Initiation of RRT or
- In pts. <18 yrs fall in eGFR to <35ml/min/1.73 m2
When is a AKI pt. referred to a Nephrologist ??
- Renal transplant
- ITU pt. + AKI (Unknown cause)
- Vasculitis/ GN/ TubuloInterstitial Nephritis/ Myeloma
- Inadequate response to Rx.
- AKI complications
- Stage 3 AKI - CKD Stage 4 or 5
- Qualify for Renal Replacement Hyper K+/ Met. Acidosis/ Uraemia complications/ Fluid overload
Risk factors of AKI ??
- Emergency Sx (ie. risk of Sepsis or Hypovolemia)
- Intraperitoneal Sx.
- CKD (if eGFR < 60)
- DM, - Heart Failure, - > 65yrs old
- Liver diseases
- Nephrotoxic drugs (NSAIDs, Aminoglycosides, ACEi/ ARBs, Diuretics
What is Pre-renal Uraemia ??
Kidneys hold on to Na+ to preserve volume
- Urine Na < 20 mmol/l
- Urine Osml > 500 mOsm/kg
- Normal/Bland sediment urine
In ATN
- Urine Na > 40 mmol/l
- Urine Osml < 350 mOsm/kg
- Brown Granular casts in urine
What is Fractional Na+ Excretion ??
What is Fractional Urea Excretion ??
- (Urine Na/ Plasma Na)/ (Urine Cr./Plasma Cr) * 100
- (Urine urea/Blood urea)/ (Urine Cr./Plasma Cr.) * 100
Rx. NOT recommended in AKI ??
- Loop diuretics
- Low dose Dopamine (to increase renal perfusion)
- Loop diuretics can only be used in Fluid overload cases
CKD classification based on eGFR ??
STAGE 1: > 90ml/min + some signs of Kidney damage on other tests (if all kidney tests normal, NO CKD)
STAGE 2: 60- 90ml/min + (same as stage1) normal U&E & No proteinuria
STAGE 3a: 45- 59ml/min + Moderate reduction in Kidney function
STAGE 3b: 30- 44ml/min + same as 3a
STAGE 4: 15- 29ml/min + Severe reduction in Kidney function
STAGE 5: < 15ml/min/ Established RF on dialysis/ Kidney transplant needed
What factors are considered to measure eGFR ??
S. Cr. - Age. - Gender. - Ethnicity
Factors that can affect are
- Pregnancy
- Muscle mass (eg. Amputees, Body builders)
- Eating RED Meat 12hrs prior to sample being takes
Common causes of CKD ??
- Diabetic Nephropathy
- Chronic Glomerulonephritis
- Chronic Pyelonephritis
- HTN
- Adult Polycystic Kidney disease
When does Anaemia becomes apparent in CKD pts. ??
- GFR < 35 ml/min or
- GFR > 60ml/min + Other causes of anaemia
- Anaemia in CKD predisposes pts. to develop LVH
Rx. of Anaemia in CKD ??
Target Hb of 10 to 12 g/dl
- Iron status should be optimised BEFORE administering Erythropoietin Stimulating Agents (ESA)
- Many pts. on Haemodialysis will require IV Iron
- ESAs like EPO & Darbepoietin used
Causes of Anaemia in CKD ??
- Reduced EPO levels (MCC)
- Reduced E-poiesis due to toxic effects of URAEMIA on bone marrow
- Reduced Iron absorption
- Anorexia/ Nausea due to Uraemia
- Reduced RBCs survival (due to dialysis)
- Blood loss due to Capillary fragility & Poor platelet function
- Stress ulceration ==> Chr. Blood loss
Ca2+ physiology seen in CKD ??
- Low Vit D (1-alpha hydroxylation normally occurs in Kidney)
- High PO4
- Low Ca2+ (due to the above 2)
- Secondary Hyperparathyroidism (due to the above 3 reasons)
Bone diseases seen in CKD ??
- Osteitis Fibrosa Cystica or Hyper-parathyroid bone disease
- Adynamic Bone disease
- Osteomalacia (due to low Vit D & high PO4 drags Ca2+ from bones)
- Osteosclerosis
- Osteoporosis
Bone disease seen with Vit D over Rx in CKD pts. ??
Adynamic bone disease
Rx. of Mineral Bone disease in CKD ??
Aim: Reduce PO4 & PTH levels
- 1st line: Reduce PO4 diet intake
- Phosphate binders
- Vit D: Alfacalcidol & Calcitriol
- Parathyroidectomy in some cases
Types of PO4 binders ??
Aluminium based (not used)
Ca2+ based Binders
- Problem: Hyper Ca2+ & Vascular calcification
SEVELAMER (MC used now)
- Non-Ca2+ based binders
- Binds to dietary PO4+ & prevents its absorption
- Other beneficial effects: Reduces Uric acid, improves Lipid profile
When is Furosemide used as an Anti-Hypertensive in CKD pts. ??
GFR falls to < 45 ml/min & it has a added benefit of lowering S. K+ levels
What is Peritoneal Dialysis ??
Form of RRT; Indications
- Stop-gap to HD or
- Younger pts. who do not want to visit hospital 3x a week
Complications of Peritoneal Dialysis ??
PERITONITIS
-MCC: Coagulase (-)ve Staph. eg- Staph. Epidermidis >Staph. aureus
Rx.-
- Vancomycin (or Teicoplanin) + Ceftazidime added to dialysis fluid OR
- Vancomycin added to dialysis fluid + Ciprofloxacin by mouth
- Aminoglycosides are sometimes used to cover the Gram (-)ve organism instead of Ceftazidime
SCLEROSING Peritonitis
MC form of Peritoneal Dialysis ??
Continuous Ambulatory P D (CAPD)
- Involves four 2-lt. exchange/ day
Approx. Equivalent values of Proteinuria ??
ACR (mg/mmol) : PCR (mg/mmol) : Urinary Protein excretion (g/24hr) =
= 30 : 50 : 0.5 g/24hrs
= 70 : 100 : 1 g/24 hrs
ACR is preferred over PCR as it has greater sensitivity
How to collect an ACR sample ??
- First-pass morning urine specimen
- If initial ACR is b/w 3 to 70 mg/mmol 2nd subsequent early morning sample should be taken for confirmation
- If initial ACR >70 mmol/l, repeat sample NOT required
Clinically significant Proteinuria ??
ACR of >= 3 mg/mmol
When to Refer to a Nephrologist
- ACR >= 70 mg/mmol unless known to be caused by DM & already appropriately treated
- ACR >= 30 mg/mmol + Haematuria (2/3 dipstick shows >= 1+ blood) + UTI excluded
- ACR: 3- 29 mg/mmol + Haematuria + RFs (declining eGFR or CVS diseases)
Rx. of Proteinuria ??
Start ACEi or ARBs
- 1st line: HTN & CKD + ACR >30 mg/mmol
- ACR >70 mg/mmol regardless of BP
