Renal Revision / vision

Year 4

The Renin - Angiotensin - Aldosterone System (RAAS)

• Activated in response to – Hypotension– Decreased sodium concentration in distal tubule– Decreased blood volume and renal sympathetic nerve

stimulation• Kidneys release renin cleaves aniotensinogen into

angiotensin I• Angiotenin I is then converted into Angiotenin II by ACE,

mostly in the pulmonary circulation• The system in general aims to increase BP

– Vasoconstriction– Increased perfusion pressure in the glomeruli (efferent arteriolar constriction)!

– Aldosterone• Na retention

– ADH release

Nephrotic SyndromeNeed all three:

1. Proteinuria (>3g/day)2. Hypobuminaemia (<30g/L)3. Oedema (pitting)

Consequences:HyperlipidaemiaThromboembolismInfection+/- Uraemia

Nephrotic Syndrome

Commonest causes:1. Membranous Glomeruloonephritis2. Minimal-Change GN3. FSGN

Nephritic Syndrome

• What is it?

–Haematuria & Protinuria

– Often HTN, oedema & oliguria

– Seen in IgA Nephropathy GN (most other GNs present with nephritic syndrome

Nephrosis

• Nephrosis refers to a non-inflammatory nephropathy

• It should not be confused with nephritis where inflammation is implied

Overview of renal disease ?From year 3

• Renal disease is common– 20% of those presenting as

emergencies will have renal disease as a secondary problem

– Up 7% of the normal population will have abnormailities of the kidneys

– The number of patients with renal failure are increasing

Note: Around 40% of those with ESRF will receive transplants

Stage Description GFR (mls/min/1.73m2)

1 Kidney damage with normal GFR

>90

2 Mild decrease in GFR

60-90

3 Moderate decrease in GFR

30-60

4 Severe decrease in GFR

15-30

5 End-Stage Kidney Failure

<15

The kidneys are predisposed to injury– <5% Total Body Weight but 20% Cardiac Output

• The larger the vascular bed in an organ the more likely it is to suffer secondary a hit of infection

– Much of the kidney is relatively ischaemic– Glomerular capillary bed on the arterial side of

circulation pressure gradient high far more sensitive to pressure changes

Overview of renal disease ?From year 3

Clearance measurement for GFR

• Inulin – Gold Standard (infused plant polysaccharide)• Creatinine (muscle – endogenous / meat –exogenous)• Cystatin C – More sensitive in “creatinine blind” early GFR loss.

Useful in prognosis

• U x V ml/min

P– Where U = concentration in urine (mmol/L)

V = volume of 24hr urine collection (ml/min)P = concentration in plasma (mmol/L)

Serum Creatinine / Clearance compared

• Serum creatinine is relatively specific but not that sensitive (need to lose a lot of kidney function before creatinine drop is registered)

• Creatinine Clearance is theoretically more sensitive but s thwarted by poor reproducibility and positive bias vs GFR.

Serial Measurements of Serum Creatinine• Normal day to day varition in individuals is much smaller

that the population reference range of serum creatinine Trends in serum creatinine in an individual can signal changing

GFR even when all results fall in the population ref. range

How do we measure kidney function?– GFR

• Creatinine– Freely filtered at glomerulus and not reabsorbed or secreted– Useful in steady state but can be inaccurate

» Dependent on muscle load» Excreted to some extent by tubules

– The MDRD is the equation to change creatinine levels to GFR» It accounts for Age, Weight, Sex and Ethnicity» Excluded: Pregnancy (use cratinine

clearance) >70 years or <18 years» An alternative is the Cockroft-Gault Equation

– Counahan Barratt Equation or Shwartz equation in children

In a person with kidney disease creatinine increased over time exponentially need to use log(1/creatinine) to give time scale for prognosis

Overview of renal disease

• Renal Failure– Acute is preferable to chronic

• 80% with acute will regain kidney function• Can’t cure chronic; just slow it down

• Polycystic Kidney Disease– Autosomal Dominant– Cysts compress normal kidney tissue– Enlarged kidneys– Abnormalities in epithelium (Polycystin Protein)– 10% of ESRF

Overview of renal disease ?From year 3

• Renal Vascular Disease– Narrowing of renal arteries kidney shrinks up– Seen in people with other CVD

• Glomerulonephritis– E.g. IgA nephropathy– Autoimmune inflammatory disease

scarred glomeruli– 15-20% of ESRF

• Diabetic Nephropathy– Microvascular Disease– Structural change within glomeruli– 20-30% of patients with ESRF

Overview of renal disease ?From year 3

Acute Renal Failure• Small vessel vasculitis• BVs inflammed all over the body

e.g. alveoli capillaries bleed into lungs • Complete obliteration of glomerulus

– Rupture & spill cells into Bowman’s Space“Crescentic” – crescents seen on LM, due to epithelial cells in Bowman’s space

Overview of renal disease ?From year 3

Post-renal Failure (Ureteric Obstruction)– Causes:

• Kidney Stone• Cancer• Retroperitoneal spaces occluding ureters

– Ascending pressure no filtration

– Treatment: • Extracorporeal Shockwave Lithotripsy• Ureteroscopic Stone Removal• Percutaneous Nephrolithotomy

Overview of renal disease ?From year 3

Manifestations of Kidney Disease (mostly Chronic Kidney Disease)

Normal Function

Regulate BP HypertenisonRegulates Salt and Water oedemaPromotes EPO AnaemiaVitamin D α1hydroxylation Bone Disease

Patients with kidney failure are at a massively increased risk of CVD, strokes and MIs (hypertension)

Overview of renal disease ?From year 3

Drugs• All patients with renal failure are on Angiotensin Blockers

• ACE inhibitors • E.g Captopril• Lower renovascular resistance• Increase Natriuresis

• Diuretics• Loop – furosemide• Thiazide• Decreased BP

If ESRF• EPO• Vitamin D• Haemodialysis or Transplant

– Outcome of dialysis is poor! – avg lifespan 3 years!!!

Overview of renal disease ?From year 3

• Filtration Barrier– Endothelium (fenestrated capillary)– Basement Membrane (negatively charged repels proteins)– Podocytes

– Limit 70000 MW• Can’t let platelets through as they would form a thrombus on contact with collagen in the basement membrane

• Filtration Fraction = 20%– Ratio of GFR to Renal Plasma Flow (RPF) – RPF = (1 - haematocrit) x Renal Blood Flow

• Renal Blood Flow ~1100ml/min– Percentage of CO to kidney (21% of 5600ml)– High as needs energy for N/K ATPase

• Renal Plasma Flow ~ 600ml/min– Plasma is ~55% of blood at a Hct of 45%

• Glomerular Filtration Rate ~120ml/min– Amount of ultrfiltrate produced / min– 180L / day

Overview of renal disease ?From year 3

• Urine Production

1ml / min

1.5 L / day

(0.8% x GFR)

• Normal Urine Osmolality 500-1000 mosmol/kgH20– In diabetes insipidus the urine osmolality is normally 60 and you

excrete 25litres per day!– If didn’t drink water for 2 hours what would the plasma osmolality

change to?• Excrete 25L / day• Therefore every hour excrete around 1L• In 2 hours would excrete 2L.• Average body has 45 litres of water• 285 x 45/43 = 298mosmol/kgH20

• Ingestion of isotonic NaCl disperses into interstitial space and blood but not cells.– The body removes it by decreasing renin release and ADH

supression – Need 3L of saline to replace 1L blood loss

Overview of renal disease ?From year 3

The schematic Nephron• Glomerulus

– Ultrafiltration

• PCT– Reabsorption

• Glucose, AAs, K+, HCO3-, Na+

• Loop of Henle– Creates medullary hyperosmolality

• DCT– Fine tuning & pH of urine drops (urinary acidification)– Na/K via aldosterone

• Collecting Ducts– Regulates volume / concentration– Under ADH control

Pathophysiological Consequences of Renal Disease

• Reduction in Glomerular Filtration Features of “uraemia” and hyperkalaemia

• Inability to release erythropoeitin Anaemia

• Inability to convert cholecalciferol to 1-αhydroxycholecalciferol (Vitamin D)Hypocalcaemia & Bone Disease

• Inability to Excrete Phosphate Renal bone disease

• Inability to excrete salt and water Hypertension & volume overload

Features of uraemia• Pruritis• Vomiting• Metallic Taste• Anorexia• Restless leg• Bone Pain

• pericarditis

Albumin : Creatinine Ratio(ACR)

• Measure of renal function used in diabetic renal disease• Use first morning sample of urine

• Microalbuminuria is defined as – ACR of > 2.5mg/mmol in ♂ and >3.5mg/mmol in ♀

or– Albumin Conc > 20mg/L

• Proteinuria is defined as – ACR >30mg/mmol

or– Albumin Conc >200mg/L

(NB: Dipsticks only pick up>250mg/L)

NB normal protein excretion is <150mg/day. This may rise to 300mg/day e.g. orthostatic, fever or after exercise

Urea : Creatinine Ratio

• Renal disease plasma urea and creatinine both increase.

• If there is a disproportionate rise it can tell you the problem

High U:C ratio Low U:C ratioHigh protein diet Low protein dietGI bleeding End stage Liver DiseaseMuscle wasting DialysisDehydrationUrinary Obstruction

Oliguria– <400ml / day– Causes:

• Decreased Renal Perfusion• Renal Parenymal Disease• Renal Tract ObstructionNB if pre-renal the cells will still be working, so Na will be reabsorbed

(low urinary[Na]) and urine will be being concentrated (>600mmol/L)

NB Course of ARF = Oliguria Diuretic Phase Recovery (sometimes)

Polyuria– ~>3L/day– Causes:

• Diabetes Mellitus• Chronic Renal Failure• Diabetes Insipidus

– Cranial (lack of AHD)– Nephrogenic

» Lithium, Genetic, Hypokalaemia, Hypercalcaemia• Psychogenic• Renal Medulla Disorders (impaired concentration of urine)

Proteinuria– Normal glomerular protein filtration 7-10g/24hrs– Normal urinary protein excretion 150mg / 24hrs– Tamm-Horsfall Protein 75mg/24hrs

(secretory protein that makes up ½ of urinary protein)

– Albumin - <30mg/24hrs(an increase in albumin is almost exclusively an intrinsic renal dx)

LimitationsDipsticks - >250mg / L albuminProtein error of indicatorsDon’t detect bence jones protein

(Multiple Myeloma, Waldenstroms Macroglobulinaemia)Microalbuminaemia– Pathological increase in urinary albumin below detection limit of sticks– Good indicator of diabetic nephropathy

Proteinuria Mechanisms• Overflow:

– Bence Jones, Hb, Myoglobulin

• Glomerular Filtration Leak:– Albumin

• Tubular:– Β2 Microglobulin

• Filtered by th glomerulus and partly absorbed by the tubules• Glomerular Dx ↑ [Plasma] & ↓ [Urine]• Tubular Dx ↓ [Plasma] & ↑ [Urine]

• Secreted:– Tamm Horsfall

NB: Test for blood shows positive for Myoglobin as it just tests for haem

Proteinuria – non-renal factors

• Strenuous Exercise• Posture

– Upright more albumin in urine– Early morning – less albumin in urine

• Fever• Burns• CCF

Glomerulonephritis

• A group of disorders where there is damage to the glomerular filtering apparatus, causing a leak of protein +/- blood into the urine.

• Patients may be assymptomatic or present with haematuria, proteinuria, nephrotic syndrome, nephritic syndrome, renal failure or hypertension.

Glomerulonephritis

• Types:– Thin Basement Membrane Nephropathy– Minimal Change GN– Membranous Nephropathy– IgA Nephropathy (Berger’s Dx)– Focal Segmental Glomerulosclerosis– Henoch-Schonlein Purpura– Proliferative GN– Mesaniocapillary GN– Rapidly Progressive GN (RPGN)

General Management of GN

• What do you do for people with GN?

– Keep BP <130/80 or >125/75 if proteinuria>1g/day

• Include ACEi or A2A

– Refer to a nephrologist!

Thin Basement Membrane Nephropathy

• Autosomal Dominant (genetic cause)

• Persistent Microscopic Haemturia

• Diagnosis: – Renal Biopsy – thin GBM on electron microscopy

• Prognosis:– Small risk of CRF, preceded by HTN & proteinuria.

(monitor1-2 yearly)

Minimal Change Glomerulonephritis (MCGN)

• Commonest cause of nephrotic syndrome children• Thought to be T-lymphocyte mediated• May also present with haematuria or HTN• Associated with Hodkin’s Lymphoma and some drugs• Tests

– selective proteinuria (only small proteins are leaked out)• Treatment

– Corticosteroids– Cyclophosphamide or Cyclosporin are used if frequent relapses

or steroid SE• Prognosis

– 1% ESRF

Membranous Nephropathy• Accounts for 20-30% of nephrotic syndrome in adults• Unknown cause• Biopsy shows thickened glomerular BM• Immunofluoescence shows IgG & C3 subepithelial

deposits• Associations:

– Malignancy, drugs (gold, penecillaine, captopril) autoimmune (RA, SLE), infections (HBV, Syphillis, Leprosy)

• Presentation – usually nephrotic syndrome• Treatment

– Corticosteroids with cyclphosphamide / chlorambucil– Based on prognostic factors (heavy proteinuria, ↓rena function

• Prognosis– Untreated 40% spontaneous remission

Focal Segmental Glomerulosclerosis• May be primary (idiopathic) or secondary (reflux, IgA nephropathy,

Alport’s Syndrome or Vasculitis)

• HIV is associated with a specific subtype

• Presentation: – nephrotic syndrome or proteinuria– 50% have impaired renal function

• Biopsy Findings:– Focal Sclerosis (scarring) of some glomeruli– IF: IgM & C3

• Treatment– 30% responds to steroids

• Prognosis– 30-50% ESRF

IgA Nephropathy (Berger’s Disease)

Dan• Commonest GN in developing world!• Presentation: Macroscopic or Microscopic haematuria• Typical Patient:

– Young male with pisodic macroscopic haematuria a few days after URTI e.g. pharyngitis. Recovery is often rapid between attacks. There is overproduction of IgA, possibly due to infection which forms immune complexes & deposits in mesangial cells.

• Biopsy– Mesangial Proliferation– IF deposits of IgA & C3

• Treatment– General measures (BP)

• Prognosis– Worse if male with htn and proteinuria– 20% develop ESRF over ~20 years

Henoch-Schonlein Purpura (HSP)• A systemic variant of IgA Nephropathy causing a small vessel

vasculitis

• Features– Purpuric rash on extensor surfaces (legs)– Flitting polyarthritis– Colic– GN

• Diagnosis– Usually clinical– Confirmed with IF IgA & C3 in skin biospy or renal biopsy

• Treatment– Nothing specific (Treat BP)

• Prognosis– 15% nephritic pts ESRF– 50% nephritic & nephrotic ESRF

Proliferative Glomerulonephritis• Classified Histologically

– Focal, diffuse or mesangiocapillary GN• The chief cause is post-streptococcal GN occurring 1-2 weeks after

a sore throat or skin infectionA streptococcal antigen is deposited on the glomerulus causing a host reaction & immune complex formation

• Presentation– NEPHRITIC SYNDROME

• Renal Biopsy – inflammatory reaction affecting mesangial and endothelial cells.– IgG & C3 deposits

• Serology– ↑ ASOT (antistreptolysin O antibodies titre)

Assists diagnosis of strepococcal infection (scarlet fever, rheumatic fever, proliferative GN)

• Treatment– Supportive >95% recover renal function

Mesangiocapillary GN• Rare• Biopsy

– Large glomeruli mesangial proliferation & thickened capillary walls tramline appearance of double BM

• Type I = Subendothelial Immune Deposits– Decreased C4 levels (classical complement pathway)

• Type II = Intramemranous Deposits– Sometimes with partial lipodystrophy (gaunt facial expression)– Decreased C3 levels (alternate complement pathway)

• Treatment– None proven

• Prognosis– 50% develop ESRF

Rapidly Progressive Glomerulonepritis (RPGN)

• The most aggressive GN with the potential to cause ESRF over days!!!

• Biopsy– Crescents affecting most glomeruli (a proliferation of epithelial cells and

macrophages in bowman’s capsule)• Causes

– Microscopic Polyangiitis (pANCA +ive)– Wegener’s Granulomatosis (cANCA +ive)– Anti-GBM dx (Goodpasture’s Disease)

• Clincally– Signs of renal failure +/- signs of the systemic disease

(e.g. fever, malaise, myalgia, weightloss, haemoptysis)

• Treatment– Aggressive Immunosuppression with high dose corticosteroids &

cyclophosphamide, with plasma exchange to remove existing antibodies

• Prognosis– Poor if initial serum creatinine >600umol/L– Below this 80% have improvement of renal function

Rapidly Progressive Glomerulonepritis (RPGN)

• Type 1 = Anti-GBM Glomerulonephritis– Antibodies directed against non-collagenous domain of the alpha-3-

chain of type IV collagen present in the basement membrane.– Some are also associated with antibodies against the basement

mebrane of the lung alveoli producing Goodpasture’s Syndrome– The majority of type I however, feature the anti-GBM antibodies alone;

these cases are considered idiopathic

• Type 2– RPGN caused by the deposition of immune complexes– Causes include SLE, Postinfectious GN, Henoch Schonlein Purpura.

• Type 3– Pauci-immune RPGN– No anti-GBMantibodies or immune complex. – Often associated with a vasculitis (wegener’s, MPA or chur-strauss)

Children with Proteinuria

• The majority of cases in children are due to minimal change GN. Therefore a course of steroids is given initially.

• Biopsy is reserved for those whose proteinuria has not reduced after 1 month, or features suggest another cause e.g. Age <1, family hx, extrarenal dx, haematuria …

Questions• What the commonest cause of nephrotic syndrome in children?

– Minimal Change Gloerulonephritis

• What’s the commonest GN in the developed world? (both names for it)– IgA Nephropathy / Berger’s Disease

• Can you be nephrotic with a normal eGFR?– YES! Early recognition of Rapidly Progressive GN is essential! Don’t

wait for eGFR to fall!!!Still needs urgent assessment and intervention i.e the classification doesn’t suit all kidney disease

• If you have CKD what are you going to die of (most likely)?– CV disease

• Atherosclerosis (inimal plaques / occlusion) + Arteriosclerosis (medial thickening / cacification)

Renal Tubular Disease• Renal Tubular Acidosis(RTA)

– a metabolic acidosis due to impaired acid secretion by the kidney. There is a hyperchloraemic metabolic acidosis with normal anion gap.

– Type 1(distal) RTA• Inability to secrete H+, and generate acidotic urine, even in states of

metaboic acidosis– Buffering of H+ in bone

Rickets / Osteomalacia Nephrocalcinosis

– Decreased Urinary Citrate (reabsorbed as buffer or H+) & alkaline urine Calcium phosphate Stone Formation

• Diagnosis:– Acid load: oral ammoniumchloride – there is failure to lower urine <pH5.5

• Treatment:– Oral Sodium Bicarbonate or Citrate

– Type 2 (proximal) RTA• “Bicarbonate leak” – defect in HCO3- reabsorption in proximal tubule.

– The tubules are able to absorb some HCO3, so urine can acidify during systemic acidosis.

– Hypokalaemia is common due to the osmotic diuretic effect of HCO3- causing flow rate to increase in the distal tubule which increases K+ excretion.

• Diagnosis– IV sodium bicarbonate load high fractional excretion of HCO3- (>15%)

• Treatment– High doses of bicarbonate

Causes of Renal Tubular Acidosis• Type 1 (distal)

– Idiopathic– Genetic (marfans, Ehlos Danlos Syndrome)– Autoimmune Dx (SLE, Sjogrens, AI hepatits)– Nephrocalcnosis (e.g. hypercalcaemia, medullary sponge kidney)– Tubulointerstial Dx (eg. Chronic pyelonephritis)– Drugs (lithium, amphoteracin)

• Type 2 (proximal)– Idiopathic– Fanconi syndrome

• Defective reabsorption of AA, K+, phosphate ( hypophosphataemic rickets / osteomalacia), glucose (glycosuria) and bicarbonate (Type 2 RTA)

– Tubulointerstitial Dx (e.g. myeloma, interstitial nephritis)– Drugs (heavy metals eg.lead, acetazolamid, out of date, tetracyclines)

Renal Tubular Disease• Renal Tubular Acidosis(RTA)

– a metabolic acidosis due to impaired acid secretion by the kidney. There is a hyperchloraemic metabolic acidosis with normal anion gap.

– Type 3 RTA• Rare combo of type 1 & 2

– Type 4 (Hyperkalaemic) RTA• Due to “hyporeninaemic hypoaldosteronism”

– Hypoaldosteronism causes hyperkalaemia and acidosis (↓K+ & H+ excretion)• Treatment

– Remove any cause» K+ sparing diuretics, NSAIDs, ACEi/A2A

– Control K+ » Fludrocortisone 0.1mg PO (aldosterone agonist), Furosemide or calcium

resonium

Hereditary Hypokalaemic Tubulopathies

• Bartter’s Syndrome– Major cause of congenital (autosomal recessive) salt wasting –

via a NaCl leak into the loop of henle via a defective channel.– Presents in childhood with failure to trive, polyuria and

polydipsia.– RAAS activation hypokalaemia and metabolic acidosis,

increased urinary K+ & Cl-

• Gitelman Syndrome– ↓ NaCl reabsorption at the distal tubule due to an autosomal

recessive mutation causing ↑ K+ loss due to secondary hyperaldosteronism. Also hypocalciuria and hypomagnesaemia.

• Haemofiltration– Hydrostatic Pressure across a semi-permeable

membrane causes movement of fluid from the high pressure to the low pressure compartment.

– Small molecules move across the membrane to maintain equal concentration

– But larger molecules are excluded to an extent quantified by the “sieving coefficient”

– Advantage• Enhances haemodynamic stability (poor evidence)

– Disadvantage• Inadequate clearance in 3 weekly sessions of 4 hours each

Haemodialysis vs Haemofiltration

• Haemodialysis– Countercurrent flow

– Vascular Access

Haemodialysis vs Haemofiltration

Middle Molecules• Β2 Microglobulin

In patients on long term haemodialysis Β2 Microglobulin can aggregate into amyloid fibres that deposit in joint spaces “Dialysis Related Amyloidosis”

• Low Molecular Weight Proteins– Peptide hormones, growth factors

• Uraemic Factors

Vascular Access– In order to haemodialyse blood must be

removed processed and reinfused at a rate of 300-400ml/min for chronic treatment

• Best achieved with an AV fistula– Radial-Cephalic, Brachial-Cephalic, Brachial-Basillic– End to End, End to side (most common), Side to side.– Non-dominant hand preferred – Can be used after 4 weeks– Palpable thrill– Avoid Pressure on fistula arm– Avoid venflons and blood test in fistula arm

Complications of Fistulae

• Thrombosis– Can be caused by patient having high / low BP– Report thrill have gone– Rx: THrombectomy &/or IV heparin

• Infiltration of vessel – “blow”– Bruising stays =/-sweeling

• Stenosis– Rx: Fistulopathy or re-anastamosis

• Aneurysm Formation• Infection• Cardiac failure• Bleeding

Other Access for Haemodialysis• AV Grafts

– Artificial blood vessel used to join an artery to a vein– Used when patients BV are too small / lots previous fistulae– Graft may be straight or looped– V. High rates of infection– V. high rates of clotting

• Central Venous Catheter– In the acute setting a Percutaneous Dual Lumen Dialysis

Catheter is inserted in a central vein (Femoral/ Internal Jugular/ Sublclavian)

• Femoral Line– High risk of infection. Restricts mobility. Have to tay in hospital

• Internal Jugular– Usual site for permacath. Line is tunnelled in. Has a cuff which sits under

the skin and secure the line in place. Patients can go home with them– Infection

• 85% of all catheter problems • Any pt with a line who presents with a temp should be treated as a

line infection until proved otherwise

Survival

• The most important correlates for survival are:– Urea reduction ratio (amount of dialysis

delivered)– Serum Albumin

• Higher is better

Peritoneal Dialysis– CAPD

• Continuous – dialysis goes on all the time• Ambulatory – pt can walk about• Peritoneum – the area in the body where the dialysis takes place• Dialysis – the process of removing solutes from circulating blood

– SA of peritoneum is roughly equal to Body Surface Area but only 1/3rd of the peritoneum is used

– Glucose in high concentration (40-150mM) is used as an osmotically active agent to achieve filtration (Na+ & H2O) across the peritoneal membrane

– Urea and electrolytes pass down concentration gradients and are cleared

– 8 to 10 litres are used as exchange per day– Disadvantages of PD:

• Adequacy of clearance relies on some residual renal function• Inadequate dialysis in large patients• Glucose load contributes to protein malnutrition and lipid

abnormalities• Allowed showers but not baths. Special pouch for swimming

Contraindications to Peritoneal Dialysis

• “Ostomies”• Dementia• Abdominal Surgery• Obesity

Diabetes is NOT a contraindication!

Peritoneal TransportThree Distinct Processes

1. DiffusionSolute move from high conc to low conc, until equilibrium is reached (generally 2 hrs later)Increase solute clearance

More frequent exchanges or larger volumes

2. Ultrafiltration

3. Fluid AbsorptionOsmosis – put in osmotically concentrated glucose solutions so water and solutes move from blood into peritoneumThe more concentrated glucose you put in the more fluid you will remove

Peritoneal Dialysis• Catheter Insertion

– Medical Insertion• Can have this is had no previous abdo surgery as adhesions would

increase the risk of perforation• LA blind procedure

– Surgical Insertion• GA exploratory / placed procedure• Inner cuff goes to rectus sheath, out cuff stays subcutaneous

– Specific Pre-operative Care• S.aureus eradication• Adequate bowel preparation• Prophylactic antibiotic cover• Identify / mark catheter exit site• Empty bladder

– Specific Post-Op Care• Immobilise and secure the catheter.• Maintain regular bowel motions

Peritoneal Catheter / Exit Site Problems• Exit site infection• Tunnel infection• Leakage

– Dipstick strongly positive for glucose• Cuff extrusion• Catheter Migration

– Upwards• Fluids in but can’t get it all out

• Other Problems– PERITONITIS– Sclerosing Peritonitis rare but 50% mortality– Herniae – due to increased intrabdo pressure– Hydrothorax– Backache– Appetite suppression– Weight gain– Psychlogical issue – body image

Automated Peritoneal Dialysis (APD)

• Overnight Peritoneal Dialysis – Typically 8-9hrs– A machine automatically fills the peritoneum with fluid

and automatically drains the fluid– The last fluid is kept in the abdomen during the day

• During the day may need top-up exchanges

Peritonitis in Peritoneal Dialysis• “Cloudy” dialysis fluid

– WCC >100 per mm3• No need for pyrexia

– Can be completely assymptomatic except for cloudy dialysis fluid

• Treatment– Broad based antibiotics (IP, Oral or IV) pending cultures– 10-14 days treatment– “severe” or “mild” protocol– Pain relief (paracetamol – pethidine)– Antibiotic monitored to maintain theraputic dose

Calcium and Phosphate Metabolism in ESRF

• Failure to α1hydroxylate vitamin DHypocalcaemia(correctable with α1hydroxylated forms of vit D)Hyperphosphataemia

HyperparathyroidismOsteoporosisKidney StonesMyopathy

Raised CaXPi productCaXPi is the only factor in ESRF which causes vascular calcification & is specifically correctable

Vasculr calcification (invariably)Tumoral Sclerosis (rare)

- Loculated masses of calcific debris & fluid enclose by fibrous tissue

- Most common in hips and buttocks and elbows

Renal Transplant

• 1954 – 1st successful human kidney transplant• Identical twins can donate between one another

and only require minor immune suppression to prevent rejection

• Transplant is the treatment of choice in ESRF• Proceedure

– New kidney is anastamosed onto the iliac vessels in the R. or L. iliac fossa.

– The native kidneys are left untouched

Renal Transplant• After 30 days post-op the patient’s risk of death becomes lower than

those on the waiting list.• Primary Benefit – Life Expectancy• Secondary Benefits

– Improved kidney function• Dietary and fluid restriction are no longer needed• Bone metabolism improved• Anaemia improved

– Psychosocial– Employment– Restoration of fertility and pregnancy

• Age is not a contraindication to transplantation. However, in the 7th and 8th decades patients often have extreme vascular disease and if so would not benefit from transplant

• Live donors give much better life expectancy / kidney functioning time than cavedric transplants

Renal Transplant• Contraindications to tranplant

– Absolute:• High peri-operative risk (CV dx etc.)• Poor life expectancy• Active malignancy

– Immune suppression will increase ca growth• Acute Infection

– Relative:• CHD• CVD• Non-compliance in previous transplantation• Recurrent disease on previous transplant

– Primary glomerular disease– Secondary systemic disease (e.g. diabetes)

Rejection of Kidney TransplantsHyperacute rejection

• Very rare with proper assessment of donor and patient blood group compatibility

• Due to preformed antibodies and compliment (ABO antibodies or species specific antigens e.g. Gal1) coming into contact with antigen expressed by epithelial cells and binding activation of immune responseFormation of Membrane Attack Complex (C5-C9) cell lysis resulting in intravascular thrombosis

haemorrhagic and thrombosed kidney in need of removal

Rejection of Kidney TransplantsAcute Allograft Rejection• Histology

– Tubulitis– Inflammatory T cells into tubules

• The kidney has a resident population of dendritic cells that egress into the blood of the recipient and go to the secondary lymphoid sites

• Direct Allorecognition Indirect Allorecognition

Passenger dendritic cells Allopeptide (graft material)presenting natural peptide presented by circulating

dendritic cells

Rejection of Kidney TransplantsAcute Allograft Rejection…• MHC class II molecule present antigen which is recognised by the T

cell receptor. The T cell then needs a second signal (e.g. B7 interacting with CD28 on the T cell surface) to become full active. This is called costimulation

• The T cell then produces new molecules such as IL2 which than binds to the IL2 receptor on the cell surface & drives the T cell into proliferation. These activated T cells lead to the activation of other cell types (such as macrophages, B cells and CD8+ T cells) that are involved in the direct destruction of the kidney transplant

.

Immune Suppression In Kidney Transplants

• Immunosuppressive drugs target one or more of the T cell activation pathways

Immune Suppression In Kidney Transplants

• Steroids– Effect against the transcription of cytokines – Modulate expression of cell surface antigens on antigen presenting cells

(APCs) • Calcineurin inhibitors

– Tacrolimus– Cyclosporin A

• TOR inhibition (“TOR” = Target Of Rapamycin)– Sirolimus

• AntiCD25 monoclonalantibodies– CD25 is an important component of the IL-2 receptor– Basiliximab– Daclizumab

• Blockage of cell cycling processes– Azathioprin (AZA)– MMF (Mycophenolate Mofetil)

Nephrotic Syndrome• If there is oedema, dipstick an MSU for protein to avoid

missing this diagnosis

• Triad:– Proteinuria (>3g/day)– Hypoalbuminuria (<30g/L)– Oedema

• Pitting, gravity dependent• Periorbital and peripherally (in limbs)• Genital oedema, ascites and anasarca (fluid in organs) occur later.

• Differential– Heart Failure– Liver Disease (decreases albumin)

Nephrotic Syndrome• It was thought that the protein loss caused the

decreased serum albumin resulting in decreased oncotic pressure & oedema. However, plasma oncotic pressure remains the same and oedema is now thought to result from Sodium Retention in the extracellular compartment & molecular changes in the capillary barrier.

• Causes– >80% are due to glomerulonephritis– Also seen in…

• Diabetes• Amyloidosis• SLE• Drugs• Allergies

Nephrotic SyndromeComplications• Susceptibility to Infection

– Due to immunoglobilin lost in urine & immunosuppresive treatments

• Thromboembolism – 40% – E.g DVT /PE / Renal vein Thrombosis– Hypercoagulable state due to increased clotting factors and

platelet abnormalities• Hyperlipidaemia

– Increased cholesterol and triglycerides due to hepatic lipoprotein synthesis in response to low oncotic pressure

General Management of Nephrotic Syndrome

• Monitor U&, BP, Fluid balance & weight regularly. The individual diagnosis should be treated individually

• Restrict salt intake• Normal protein intake is advised• Diuretics often used

– e.g. furosemide 80-250mg/day PO• Chronic Nephrotic Syndrome

ACEi decrease proteinuria and slow progression or renal impairment

• Prophylactic Heparin if mobile• Treat Hypertension• Persisting Hyperlipidaemia should be treated with a

statin.

Renal Vein Thrombosis• The hypercoagulable state of nephrotic syndrome

predisposes to renal vein thrombosis (mostly in membranous nephropathy)

• Other causes include– invasion by renal cell carcinoma– thrombophillia

• Clinically– Often assymptomatic, but may present with loin pain, haematuria,

palpable kidney, sudden deterioration in renal function.

• Diagnosis– Doppler USS, CT, MRI or renal angiography (venous phase)

• Treatment– Anticoagulate with warfarin for 3-6 months (until albumin >25g/L)

• Target INR is 2-3

Renal Artery Stenosis• Causes:

– Atherosclerosis (50 or >)– Fibromuscular Dysplasia (young)

• Hypertension and atrophy of the affected kidney may result renal failure

• Symptoms /Signs– Mostly asymptomatic– The largest problem is uncontrollable (refractory) hypertension due the

kidney thinking there is hypotension activates RAAS• Diagnosis

– Refractory Hypertension– Auscultation – bruit inferior of costal margin– “Captopril challenge test”

• Measure change in renin-plamsa level in response to captopril• Best for children• Positive test if renin increases substantially or baseline renin is abnormally

high– Renal Artery Arteriogram

• Rx:– Angioplasty +/- stenting

Acute Renal Failure• Epidemiology

– 200 per million per year (30% severe)– 70% occur in hospital– 5% of hospital admissions – Mulitfactorial in large majority of cases

• Risk Factors– Pre-exiting renal disease– Diabetes– Nephrotoxic Drugs / Polypharmacy– Infection– Haemodynamic Insult

• Creatinine lags behind clinical course so need to check creatinine for 5 days following possible ARF triggers

Acute Renal Failure• Definition: A significant deterioration in renal function occurring over hours

or days• You do not need a normal baseline renal function to get ARF

– ↑ Creatinine by 50% if baseline creatinine <100– ↑ Creatinine by 25% if baseline creatinine >150– Acute deterioration in renal function requiring dialysis

• Clinically there may be no symptoms or signs but oliguria (<400ml/24hrs) is common

• Biochemically ARF is detected by rising plasma urea and creatinine

• ARF may occur as an isolated problem but more often it occurs in the setting of circulatory disturbance (e.g. Severe sepsis, severe illness, trauma or surgery) or in the context of nephrotoxic drugs

• It causes a decline in GFR, perturbation of Acid / Base balance and electrolytes & ECF and accumulation of nitrogenous waste

Acute Renal FailureCauses• Pre-renal Failure

– Renal Hypoperfusion• Hypovolaemia, Sepsis, CCF, liver cirrhosis, renal artery stenosis, NSAIDs or ACEi (these interfere

with renal blood flow)

• Intrinsic Renal Failure– Acute Tubular Necrosis (ATN)

• This is damage to the renal tubular cells caused by ischaemia or nephrotoxins• Recovery of renal function occurs in weeks but mortality is high – 50%!!!

– Vascular• Vasculitis, Malignant Hypertension, Cholesterol Emboli, Haemolytic Uraemic

Syndrome, Thrombotic, Thrombocytopaenic Purpura– Glomerulonephritis– Toxic – Multiple Myeloma– Interstitial Nephritis

• De to drugs, infections, immune disroders– Hepatorenal Syndrome

• Occurs in 18% of cirrhotic patients ascites, splanchnic arterial vasodilation. ↓ Effective Circulating Volume, intense renal vasoconstriction. ↓ GFR and normal renal histology!

• Post-Renal Failure– Urinary Tract Obstruction

• Stones / BOO (Prostate) / Haematoma / Trauma / Cancer

Acute Tubular Necrosis and Hypoperfusion account for >80% of ARF

Acute Renal Failure• Acute Tubular Necrosis (ATN)

– This is damage to the renal tubular cells (renal tubules become vacuolated) caused by ischaemia or nephrotoxins

– Recoverable by dialysis– The presence of what pathgnomic sign is seen in the urine during urinalysis is

pathognomic of ATN• “muddy brown casts” of epithelial cells

– Recovery of renal function occurs in weeks but mortality is high – 50%!!!

• Acute Interstitial Nephritis– Inflammation and oedema of the interstitium– Generally allergic reaction– Up to 5% of ARF (drugs e.g. NSAIDs, PPIs)– Sterile Pyuria– Rx – stop drug and oral steroids

• Multiple Myeloma– Definition: Proliferation of a clone of plasma cells– Screen all patients with renal impairment– Renal failure with normal or increased calcium– Diagnosis often made on biopsy– Excessive light chain Ig (lambda or kappa)

• Precipitate to form casts in renal tubules

Acute Renal FailureNephrotoxins (cause ATN)Exogenous

– NSAIDs– Antimicrobials (“GAS VAT”)

• Gentamycin, Amphoteracin, Sulphoamides, Vancomycin, Aciclovir, Tetracyclin)

– IV contrast– Anaesthetic Agents – enflurane, methoxyflurane– ACEi & A2As– Cisplatin– Heavy Metal Poisoning– Organic Solvents (ethylene glycol, carbon tetrachloride)– Insecticides, Herbicides, Amanita Muschrooms, Snake Venom

Endogenous– Pigments e.g.Haemoglobinuria in haemolysis, Myoglobin in

rhabdomyolysis – Crystals e.g urate– Protein e.g Ig light chains in myeloma

Management of ARF• What should be urgently excluded?

Inflammatory Renal Diseases (RPGN) and Obstruction CRP & Urgent Renal USS

• Obstruction hydronephrosis lithostomy tube• Urine - M,C&S• Beware K+

– Hyperkalaemia• ECGIV Calcium Carbonate IV insulin & glucose (K+ and glucose are co-transported into cells)Salbutamol Nebuliser

• Stop Nephrotoxic drugs• CXR

– Pulmonary OedemaSit up and give high flow O2Venous Vasodilator e.g.morphineFurosemide 120mg IV over 1hr

If urine protein + and blood + culture MSU. If no significant growth refer to a nephrologist for exclusion of glomerulonephritis

If urine protein ++ and blood negative refer to a nephrologist for consideration of renal biopsy

Indications for Dialysis in ARF

• A: Acidosis• E: Electrolytes (K+)• I: Intoxication (methanol, ethylene glycol,

isopropanol, theophylline, lithium, salicylates)

• O: Volume Overload• U: Uraemia (pericarditis, seizures,

encephalopathy)

Distinguishing Pre-Renal Failure & ATN

Prerenal ATN• Urine Na (mmol/L) <20 >40• Urine Osmolality >500 <350• Urine/plasma Urea >8 <3• Urine / Plasma Creatinine >40 <30• Fractional Na excretion<1 >2

*In pre-renal failure urine is concentrated and Na reabsorbed by working tubular cells. This fails to happen in ATN.

Assessing whether renal failure is acute or chronic

Suspect Chronic RF if:1. History of comorbidity (e.g.diabetes, HTN)2. Previously abnormal blood tests3. Small kidneys on USS (<9cm) with

echogenicity

Chronic Kidney Disease• Definition: Presence of kidney damage for >3 months

– Blood, urine or imagingor

– GFR <60ml/min/1.73m2 for >3 months

• It is an emerging public health problems– Significant CV risk (3x)– Early intervention halts CKD– GFR is gold stnd indicator of CKD

• Risk Factors– Obesity– Smoking– Diabetes– Hypertension– Male– Older– Afrocarribean

Chronic Renal FailureChronic Renal Failure (or chronic kidney dx) is classified into 5 stages

Stage GFR1 >902 60-893 30-594 15-305 <15

Symptoms usually occur once stage 4 is reached– ESRF occurs when dialysis or

transplant is required to prolong life

Causes• Glomerulonephritis• Interstitial Nephritis• Diabetes• Renovascular Dx• Hypertension• Chronic Pyelonephritis• Prostatic Hypertrophy (BOO)• PKD• Analgesic Nephropathy• Nephrolithiasis

Rarer cause• Amyloidosis• Myeloma• SLE• Scleroderma• Vasculitis• HUS

• Gout• Alport’s

Syndrome

History Taking in suspected CRF

• Ask about: – past UTI– known HTN– Diabetes– Family Hx

• Take careful drug hx– NSAIDs, Cisplatin, Gentamycin, ACEi, enflurane

• High urea symptoms (>40mml/L)– Fatigue, weakness, anorexia, vomiting, metalic taste, pruritis,

restless legs, bone pain

• Dyspnoea and Ankle Swelling

Investigating of CRF• Bloods

– ↓Hb (Normocytic normochromic anaemia)– ESR– U&E– Glucose (DM)– ↓ Calcium & ↑ Phosphate, ↑ alk phos (renal osteodystrophy)– ↑PTH (Hyperparathyroidism 2 to ↓calcium)

• Urine– MC&S– Dipstick– Urine PCI or 24hr urinary protein

• Imaging– Renal USS– CXR (cardiomegaly, pleural / pericardial effusion)– Bone x-ray (may show renal osteodystrophy)

• Biopsy (if cause unclear & normal sized kidneys

Renal Osteodystrophy is poor bone mineralisation 2˚ to HPT, 2˚ to CRF where there is ↓ Ca & ↑ PO4

- “rugger juersey spine”

Refer urgently if GFR <30

Refer same day if GFR <15

Other Markers of CRF

• Urinary microscopy• Specific cell types in urine

– Podocytes– CD14+ cells (macrophages)– CD56+ cells (NK cells)

• LMW proteins– β2 microglobulin, retinol bindingprotein.

• Tubular Injury Marker– N-actyle- β- D-glucosaminidase (NAG)

Chronic Renal Failure• Treat reversible causes

– Relieve obstruction– Stop nephrotoxic drugs– Deal with calcium &CV risks

*In stage 1 & 2 CRF change of CV death is greater than reaching ESRF• Hypertension

– Even a small drop in BP may save significant function– ACEi & A2A can decrease the rate of loss of function, even if blood

pressure is normal!– Aim for BP <130/80 (<125/75 if 1g proteinuria / day)

• Oedema– This may require high doses of loop diuretics & restriction of fluid intake

• HyperLipidaemia– statins

• Renal osteodystrophy– Treat if ↑ PTH.– Restrict dietary PO4. (cheese, eggs, milk). Give binders e.g. calcichew

to bind PO4 in the gut– Vitamin D analogues (eg. alfalcacidol = 1hydroxycholecalciferol) – Calcium supplements

Chronic Renal Failure• Some patients with CRF lose renal function at a

constant rate. This is used to monitor renal function and monitor need for dialysis

• Rapid decline in renal function greater than that expected my be due to:– Infection– Dehydration– HTN– Metabolic Disturbance (Calcium)– Obstruction– Nephrotoxins

Kidneys and Bone Disease• Reduced phosphate excretion • Reduced active Vit D production

(due to less 1αhydroxylase) reduced calcium absorption

• Low Calcium & high phosphate cause… Hyperaparathyroidism Osteoclast bone reabsorption

• Features of Renal Osteodystrophy– Chondrocalcinosis at the knees and pubic symphisis– Osteopenia– Bone fractures

Back to Chronic Renal Failure

Polycystic Kidney Disease

1. Autosomal Dominant Polycystic Kidney Disease

- Commonest inherited nephropathy 1:400-1:1000- Presents in adulthood- Characterised by multiple renal cysts- Extrarenal associations e.g. Cardiac and hepatic

2. Medullary Cystic Disease3. Medullary sponge kidney

Pathogenesis of ADPKD• Mutated PKD1 gene (85%)• Mutated PKD2 gene: majority of remaining

cases• PKD1 protein “Polycystin 1”

– Integral membrane glycoprotein– Functions as mechanosensor

• PKD2 protein – Ca2+ ion channel

• PKD1 protein and PKD2 protein work together

• Formation of multiple renal cysts from the tubules throughout the nephrons

ADPKD PresentationFeature CauseAcute loin pain +/- haematuria

Haemorrhage CystCyst InfectionUT calculi

Loin/ abdo discomfort Enlarged kidneys

SAH Berry aneurysm rupture

Complications of HypertensionComplications of liver cysts

Symptoms of uraemia Chronic Renal Failure

Erythaemia (rare)

Natural History• Progressive renal impairment• Renal Failure• Acute episodes of loin pain and haematuria• Hypertension

• Patients with PKD2 generally have a slower progression – Renal cysts are slower to develop– End stage renal failure develops 10-15 years later

than in PKD1 mutation• Men reach ESRF 5-6 years earlier than females

Diagnosis of PKD

• O/E – Enlarged irregular kidneys

+/ Hepatomegaly

• USS Definitive diagnosis

Complications of PKD• Chronic Renal Pain

– Surgical decompression / Laproscopic cyst decortication• Progressive Renal Failure

– Most serious complication, poor prognosis– Once GFR <50ml/min, annual decline is ~5ml/min/year

• Cyst Infection– Lipophilic abx against gram negative bacteria

e.g. fluooquinolones, cotrimoxazole• Renal Calculi

– Radiolucent. Percutaneous stone removal. Extracorporeal Lithotripsy• Hepatic Cysts

– Rarely, enlarged polycystic liver– Pain and infection of cysts– Surgical intervention: drainage fenestration

• Hypertension– V. common early feature. – Due to intra-renal activation of the renin-angiotensin system– Treat early >>morbidity & mortality of pts

• Intracranial “Berry” Aneurysm– Ix: Contrast enhanced spiral CT or MR angiography– Screening recommended in pts 18-40 yrs with +ve family hx

• Mitral Valve Prolapse

PKD Screening

• Offered to children and siblings of pts– Genetic screening ; all ages– USS in >20s

• Patients regularly check for HTN

• Should be offered genetic counselling

Management

• No therapy currently licensed

• Vasopressin receptor antagonists– Shown promise in animal models– Halt cyst formation

• Adenylcyclase agonists

• cAMP inhibitors

Uraemic Emergencies:Usually require urgent dialysis

• Hyperkalaemia (K+ >6.5mmol/L) refractory to medical therapy. Usually metabolic acidosis

• Severe pulmonary oedema refractory to medical therapy

• Uraemic encephalopathy• Uraemic Percarditis

* Look up Uraemic Syndrome!

Hamolytic-Ureamic Syndrome (HUS)

Triad– Haemolytic Anaemia– Acute Renal Failure (ureamia)– Thrombocytopaenia

Peak incidence 6 months – 4 years. The classic childhood case occurs following blood diarhhoea caused by a specific E.Coli 0157 that expresses verotoxin. The toxin enters the bloodstream and damages endothelium in the kidney and elsewhere causing ARF and platelet consumption. These platelets narrow the vessel which destroys RBCs by “microangiopathic haemolysis”

Note: Coagulation factors are not consumed in HUS in contrast to DIC and D-dimers a generally normal.

Adult HUS is an uncommon outcome of HIV, antiphospholipid syndrome with SLE, post-partum renal failure, malignant hypertension, scleroderma and some drugs (mitomycin, ciclosporin, cisplatin and bleomycin).

Familial HUS – accounts for 5-10%

Rx:NOT antibiotics – they can further stimulate verotoxin productionNOT platelet transfusion Supportive; dialysis if needed or plasma exchange

The Kidney and Systemic Disease

Systemic Diseases affecting the kidney– Diabetes– Inflammatory Disease

• Vasculitis, SLE, Rheumatoid arthritis– Infection

• HIV, Hep C with cryoglobulinaemia, HUS– Malignancy

• Myeloma, amyloid & paraproteinaemia, paraneoplastic membranous nephropathy

– Pregnancy

Diabetic Nephropathy• Renal disease occurs in 40% of type 1 diabetics (similar in type II)• Some type 2 diabetics are at a greater risk e.g. Pima indians,

Afrocarribeans• 40% patients with ESRF in US and 20% in Europe

• Pathogenesis– Glomerular Hyperfiltration– Thickening of Glomerular Basement Membrane– Hyperglycaemia & AGEs (Advanced Glycation End Products) promote

mesangial proliferation and matrix production resulting in Nodular Sclerosis (kimmelsteil Wilson Nodules) which generally correlates with creatinine clearance

– Eventually this progresses to Glomerulosclerosis, which is promoted by intraglomerular hypertension +/- ischaemic changes

– Cytokine Environment• Activation of cytokines such as TGF-β and VEGF promote matrix

production

Natural Hx of Diabetic Nephropathy

Screening for Microalbuminaemia

• Intervention reduces risk of progression• Microalbuminaemia is also an individual irks

factor for CV disease• Can occur transiently

– Fever, UTI, CCF, Exercise, Orthostatic

• Rx:– ACEi– Good Glycaemic Control– Hypertension control– Treat Hyperlipidaemia

The Kidney and Infection• HIV commonly affects the kidney with up to 60%

of renal biopsies showing Focal Segmental Glomeulonephritis (FSGN), the primary form of HIV nephropathy. Renal failure might also occur due to the drugs used to treat HIV such as amphoteracin and foscarret.

• Hep C may cause membranoproliferative glomerulonephritis, often associated with essential cryoglobulinaemia. The pathogenesis appears to be related to deposits of immune complexes containing anti-HCV & HCV RNA in the glomeruli.

The kidney and Malignancy• Renal disease is common in myeloma with

between 20-50% of patients with renal dysfunction, which is important as renal failure is an important predictor of mortality. Light Chains are toxic to the tubules and aggregate with Tamm-Horsfall protein (a protein normally produced by the tubular cells to form obstructing casts. This is exacerbated by dehydration often caused by hypercalcaemia. Unfiltered lambda light chains may deposit in the kidney as amyloid.

The Kidney and Pregnancy

• Profound changes occur in the urinary system:– GFR increases by 30-50%

• Fall in serum creatinine. A creatinine of 100 in a pregnant lady is profoundly abnormal!

• Renal diseases associated with pregnancy include pre-eclampsia, pregnancy induced hypertension, UTI, AFR due to post-partum haemorrhage and in those with chronic renal failure pregnancy is likely to exacerbate this.