Themed Week 8 - Renal

8/10/2019 Themed Week 8 - Renal

1/18

THEMED WEEK 8:INVESTIGATION OF ABNORMAL RENAL FUNCTION

GLOMERULONEPHRITIS

T E R M S

Focal only a portion of glomeruli affected

Diffuse all glomeruli affected

Global whole glomerulus affected

segmental only a part of the glomerulus is affected (mostfocal lesions are also segmental)

proliferative ^cell numbers due to hyperplasia of one or more of theresident glomerular cells

membranealterations capillary wall thickening

crescent formation epithelial cell proliferation with mononuclear cellinfiltration in Bowmans space


2/18


1. Common cause of ESRF in adults2. Inflammation of the glomeruli and nephrons which leads to;

a. Damage to the glomerulus restricts blood flow, leading to compensatory ^BPb. Damage to the filtration mechanism

allows protein and blood to enter urine.c. Loss of the usual filtration capacity leads

to acute kidney injury3. Looking for degree of damage and potential cause

a. Blood: FBC, U&E, LFT, ESR, CRP;immunoglobulins, electrophoresis,complement (C3, C4); autoantibodies(p555): ANA, ANCA, anti-dsDNA, anti-GBM; blood culture, ASOT, HB s Ag , anti-HCV (p406).

b. Urine: RBC casts, MC&S, Bence Jonesprotein, ACR (see p286).

c. Imaging : CXR, renal ultrasound.d. Renal biopsy

Presentation Diagnosis Treatment PrognosisIgA Nephropathy altered regulation

of IgA ^IgA possibly due

to infection, whichforms immunecomplexes anddeposits inmesangial cells.

Common cause of GNin adults

Young man (20-30 yo),Asians and Caucasianswith episodicmacroscopichaematuria, recovery isoften rapid betweenattacks

Mesangialproliferation,immunofluorescence (IF) showsdeposits of IgA andC3

Control BPwith ACEi,immunosuppression mayslow declineof renalfunction.

~20% -> ESRF.POORprognosis:Male, BP,proteinuria orrenal failure atpresentation.

Henoch-SchonleinPurpura (HSP)Systemic IgAnephropathy, causing asmall vessel vasculitis.

purpuric rash onextensor surfaces

Arthralgias Purpura Abdominal pain, GI

bleeding Hematuria

+ IF for IgA and C3in skin or renalbiopsy.

same as IgAnephropathy

~15% -> ESRF.If bothnephritic andnephrotic 50%-> ESRF

Systemic lupuserythematous (SLE)

Cough, chest pain, nasal congestion Maculopapular rash over her chest Haematuria, proteinuria,

~1/3 SLE have renal diseasewith vascular, glomerular andtubulointerstitial damage.

Anti-glomerularbasement membrane(GBM)A.k.a. Goodpasturesdisease caused byauto-antibodies to type

Pulmonaryhaemorrhage

Haematuria/nephiritcsyndrome

AKI may occur withindays of onset of

A/b develop against3 chain type IV

collagen in GBM.Linear deposition ofIgG along GBMA/b detected by

Plasmaexchange,steroids,Cyclophosphamide

Relapse arerare. Prognosisis poor ifdialysis-dependentpresentation.


3/18


IV collagen an essentialcomponent of the GBM

symptoms Malaise, fatigue,

anorexia, weight loss,arthralgias, myalgias

ELISAANCAcapillary loopstaining with IgGand C3 andextensive crescentformation

Post-streptococcalStrep. Ag is depositedon the glomeruluscausing a host rxn andimmune complex form.

Occurs 1-12 wks aftera sore throat or skininfection

Nephritic syndrome

Urinalysis Inflammation

rxn affectingmesangial andendothelial cells

IF: IgG and C3deposits

^ASOT ^C3

ComplicationSevere HPT,renal failure,primarydisease (SLE)

Rapidly progressiveMost aggressive GN.Could cause ESRF overdays.

AKI +- systemicfeatures (fever,myalgia, weight loss,haemoptysis)

Pulmonaryhaemorrhage is thecommonest cause ofdeath

ANCA +vepatients

Aggressive immunosupresionwith high-dose IV steroids andcyclophophamide +- plasmaexchange- 5 year survival 80%


4/18


NEPHROTIC SYNDROME

Criteria

PROTEINURIA (> 3.5 G/DAY/1.73 M 2) OEDEMA- Structural damage to the glomerular

basement membrane leads to anincrease in the size and number ofpores -> allow more and largermolecules.

- Fixed negatively charged componentsare present in the glomerular capillarywall, which repel negatively chargedprotein molecules.

- Reduction of this fixed charge occurs inglomerular disease and appears to be akey factor in the genesis of heavyproteinuria.

- Expansion of the interstitial

compartment is secondary to theaccumulation of sodium in theextracellular compartment.

- This is due to an imbalance betweenoral (or parenteral) sodium intake andurinary sodium output, as well asalterations of fluid transfer acrosscapillary walls.

- Elevated TNF- levels in nephroticsyndrome activate protein kinase C,which changes phosphorylation ofoccludin and capillary permeability

HYPOALBUMINAEMIA (< 3.5G/DL) HYPERLIPIDAEMIA (C > 250 MG/DL)- Urinary protein loss of the order 3.5g

daily or more in adult required to causehypoalbuminaemia

- Increased of catabolism of reabsorbedalbumin in the proximal tubules thoughactual albumin synthesis is increased.

- Hyperlipidaemia is the consequence ofincreased synthesis of lipoproteins inthe liver, abnormal transport ofcirculating lipid particles, and decreasedcatabolism.

Nephrotic syndrome is NOT a diagnosis. Therefore, the underlying cause should always be sought.

Histological patterns of NS1. Minimal change disease

PAEDS: common cause, MALE good prognosis. X leads toCKD,facial oedema

ADULT: asso. With drugs (NSAIDs, lithium, antibiotics(cephalosporins, rifampicin, ampicillin) , bisphosphate andsulfasalazine ) or paraneoplastic (Hodgkins lymphoma)

Glomeruli appear normal on light microscopy but on EM,fusion of podocytes could be seen

Tx: high dose corticosteroid therapy with prednisolone 60mg/m 2 daily (up to a maximum of 80 mg/day) for amaximum of 4 6 weeks followed by 40 mg/m 2 every otherday for a further 4 6 weeks corrects the urinary proteinleak in more than 95% of children

Two-thirds children have relapse and further courses of corticosteroids are required. One-third of these children regularly relapse on steroid withdrawal, so that cyclophosphamide

should be added after repeat induction with steroids. A course of cyclophosphamide 1.5 2.0mg/kg daily is given for 8 12 weeks with concomitant prednisolone 7.5 15 mg/day.


5/18


2. Membranous nephropathy (common cause, 20-30% in adult) 75% are primary or idiopathic form but can be associated to 2 to drugs (penicillamine, gold,

NSAIDs, probenecid, mercury, captopril), autoimmune disease (e.g. SLE, thyroiditis), infectiousdisease (e.g. hepatitis B, hepatitis C, schistosomiasis, Plasmodium malariae ), neoplasia (e.g.carcinoma of lung, colon, stomach, breast and lymphoma) and other causes (e.g. sarcoidosis,kidney transplantation, sickle cell disease)

At all stages, IF shows the presence of diffusely thickened GBM of IgG and C3 COMMON: Adults, males Asymptomatic proteinuria or frank nephrotic syndrome. May present with mocroscopic haematuria, hypertension and/or renal impairment POOR PROGNOSIS: HPT and higher degree of renal impairment 40% develop CKD GOOD PROGNOSIS-> Younger, females, and asymptomatic proteinuria of modest degree 3 stages

Early: deposits are small can be missed on LM. EMreveals small electron-dense deposits in the sub-epithelial aspects of the capillary walls

Intermediate: deposits are encircled by basementmembrane => appearance of spikes ofbasement membrane perpendicular to thebasement membrane on silver staining

Late: uniform thickening of the capillarybasement membrane

3. Mesangiocapillary GN Immune complex (IC)

Driven by circulating immune complexes, whichdeposit in the kidney and activate complement via the classical pathway. An underlying causecan be found in most cases, eg Hep C, SLE and monoclonal gammopathies.

Complement mediated Less common and involves persistent activation of the alternative complement pathway

BIOPSY: mesangial and endocapillary proliferation, a thickened capillary basement membrane,double contouring (tramline) of the capillary walls . IF can show Ig staining, complementstaining or light chains depending on cause. EM shows electron dense deposits.

4. Focal segmental glomerulosclerosis May be 1 or 2 (VUR, IgA nephropathy, Alports syndrome, vasculitis, sickle -cell disease) Presentation: nephrotic syndrome or proteinuria. ~50% have impaired renal function. BIOPSY:scarring of the glomeruli at certain segments (focal sclerosis). IF: IgM and C3 deposits at

affected area. Tx: corticosteroid. Resistant: cyclosphamide or ciclosporin Untreated most progress ESRF

ComplicationA. DVT

a. Hypercoagulable state due to urinary losses of anti-thrombin and thrombocytosis

b. Exacerbated by steroid therapyc. Increased synthesis of clotting factors


6/18


d. Increased blood viscosity from the raised haematocrite. This is usally arterial and may affect the brain, limbs, and splanchnic circulation.

B. Sepsisa. Serum: IgG, complement, T cell functionb. Steroid: immunosuppressant toxicity

C. Lipid abnormalitiesD. HypovalaemiaE. Acute renal failure (rare)

Investigation

DIAGNOSTIC1. Proteinuria +1> on 2/3 dipstick2. P:C (> 200mg/mmol) (early morning)3. Serum lipid4. C3 level (sensitive n specific if other than

MCD)5. BP

FURTHER INVESTIGATION6. Full blood count: HCT, WBC7. Renal profile: normal in MCD

U+Es; Creatinine 8. Serum albumin:


7/18


RECURRENT UTI Same symptoms No fixed definition of recurrent

2 infections in 6 months

3 infections in 12 months After a single UTI there is a 30% risk of

recurrence with 6 months 60% will be the same organism (E coli most

common) After a first UTI 30-40% of patients will go onto

have recurrent infections Complicated or uncomplicated

Complicated: underlying anatomical orphysiological abnormality

Uncomplicated: normal urinary tract Complicated UTIs are more likely to

recur but Most recurrent infections occur in

otherwise healthy women with anormal urinary tracts

Investigations Confirm infection dipstick and MSU Other conditions can mimic infection

Confirm antibiotic sensitivities History of previous antibiotic use Ultrasound is the most useful non-

invasive investigation Treatment

Be aware of the risk of resistance Non-antibiotic treatments

Cranberry juice Increase fluid intake Probiotics Regular and/or post coital

complete voiding Avoid spermicidal

use/diaphragm Topical oestrogens

Antibiotics Long-term prophylaxis (1-2

yrs) Low dose, at night Single post-coital antibiotic

dose Self-treat


8/18



9/18


CHRONIC RENAL FAILURE1. CRF is a progressive tissue destruction with permanent loss of nephrons and renal function.

2. Definition Impaired renal f(x) >3 months based on abnormal structure or function or GFR3 months w/ or w/o evidence of kidney damage

3. ESRF: GFR


10/18


Acute renal failure Prior to dosing drugs w/ significant toxicity that are excreted by the kidneys

8. Stages of CKD

9. Risk factors

Worse renal function - higher serum creatinine Proteinuria - the higher, the greater the risk of progression Hypertension - the higher, the greater the risk Young age - they have longer for trouble to develop Renal biopsy shows fibrosis, or continuing inflammation

10. Causes of frequent causes of acute decline in GFR Volume depletion Intravenous radiographic contrast Selected antimicrobial agents (for example, aminoglycosides and amphotericin B) Nonsteroidal anti-inflammatory agents, including cyclo-oxygenase type 2 inhibitors Angiotensin-converting enzyme inhibition and angiotensin-2 receptor blockers Obstruction of the urinary tract

11. Investigation Check previous renal function Identify and treat underlying cause if possible - Renal biopsy Renal imaging

May establish cause May confirm CKD e.g. if kidneys small May identify reversible causes e.g. RAS

Identifying complications Blood tests

12. Treatment of advanced CKD or failed endocrine function

Clinical features Treatment

Salt and water OedemaHPT

DiureticsAnti-HPT

Hyperkalaemia ArrhythmiasSudden death

DietAnalysis

Acid-base Acidaemia BicarbonateHyperphosphataemia Itching Diet and binders

Erythropoietin Anaemia EPO and iron

Stage GFR Description Treatment stage

1 90+Normal kidney function but urine or other

abnormalities point to kidney diseaseObservation, control BP and CV risk

factors

2 60-89Mildly reduced kidney function, urine or other

abnormalities point to kidney diseaseObservation, control BP and CV risk

factors3 30-59 Moderately reduced kidney function Observe, BP control, RF

4 15-29 Severely reduced kidney functionPlanning for ESRF, anaemia, Ca,Pi and

PTH management

5


11/18


Decreased 1,25 Vit D Raised PTH Vitamin D

RENAL REPLACEMENT THERAPY1. Aim to identify patients with progressive CKD early 2. Timely planning for RRT

3. Options and choicesa. Kidney transplantb. Dialysis

i. Peritoneal dialysisii. Haemodialysis

4. Conservative care

HAEMODIALYSIS1. Acute indication for dialysis

A: Acidosis (metabolic acidosis) E: Electrolyte Abnormalities (hyperkalemia) I: Ingestants/Toxins (lithium) O: Overload (volume overload causing respiratory distress) U: uremia (systemic effects uremic encephalopathy, uremic pericarditis)

2. Access to circulation Central venous dialysis catheter

Temporary Risk of infection

Permanent Arterio-venous fistula Arterio-venous graft

3. Peritoneal dialysis Continuous Ambulatory Peritoneal Dialysis (CAPD)

An exchange takes about 30 minutes. Most CAPD patients need to do between 3 and 5 exchanges a day.

Automated peritoneal dialysis (APD) Rapid dialysate exchanges overnight (uses an automated device) In the morning, the patient disconnects from the machine.


12/18


4. Haemodialysis vs peritoneal dialysis

HD PD

4hrs x 3/week Duration Continuous or at nightHospital or home Place Home

Venous access

Infection

Complication Peritonitis

Exit site infection

KIDNEY TRANSPLANT1. Improved patient survival (87% vs 30% 5 year survival)2. Correction of metabolic consequences of renal failure3. Improved quality of life for patient and family4. Cost5. Cold ischaemic time - the time the donor organ was kept outside the body on ice6. Graft prognosis

Directly related to source of donor kidney. Recipients of cadaveric kidneys have more episodes of rejection and lower graft survival rates. Graft survival rates for kidneys from living donor is 95% @ 1 year and 76% @ 5 years versus graft

survival from a cadaveric kidney donor is 89% @ 1 year and 61% @ 5 years.


13/18


ACUTE KIDNEY INJURY

1. Defined as rapid reduction in kidney function over hours to days. It is common especially in ageingpopulation and AKI prone.

2. It has HIGH mortality and REVERSIBILE NEED TO RECOGNISE EARLY!!3. Criteria

Rise in creatinine > 0.3mg/dL (>26mol/L) in 48 hours Rise in creatinine >1.5 x baseline (best figure in last 3/12) Urine o/put 6 consecutive hours

4. Staging for AKI

K I D

N E Y

Excretion of waste productsnitrogen-containing waste products e.g. urea

EPO (erythropoietin) productionstimulates red cell production

Vitamin D metabolismhealthy bones

Homeostasissodium and water balance

electrolyte balance; phosphate, potassiumacid-base balance


14/18


5. Consequences of sudden loss of renal function/presentation of AKI

ACCUMULATION OF TOXINSACCUMULATION OF

SALT & H2Ourea and other uraemic toxins

nausea, vomiting, malaise pericarditis, pleurisy fitting increased bleeding risk increased infection risk

metabolic acidosis

haemodynamicinstability

disruption ofcellular f(x)

potassium

muscleweakness

cardiacinstability

fluid overload

(hypertension)

6. Risk factors: Age >75 CKD Cardiac failure Peripheral vascular disease Chronic liver disease

Diabetes Drugs (esp newly started) Sepsis Poor fluid intake/ increased losses Hx of urinary sx

7. Causes

Impaired perfusion of the kidneys with blood, eg hypotension (hypovalaemia,sepsis)

Due to cardiac failure, blood loss, dehydration, vascular occlusion, hypotension,impaired cardiac pump efficiency or vascular disease limiting renal blood flow, orcombinations of these factors.

Drugs which impair renal autoregulation; ACEi and NSAIDs

Pre-renal - not enuf blood at suff. pressure to allow filtering

TUBULAR: ATN is the commonest cause, often a result of pre-renal damage ornephrotoxins (aminoglycaside, radiological contrast, myoglobulinuria)

GLOMERULAR: a/immune; SLE, lymphoma, infection, 1' glomerulonephritidesINTERSTITIAL: drugs. infiltration with, eg lymphoma, infection, tumour lysissyndrome following chemotherapy

VASCULAR: vasculitis, malignant HPT, thrombus, large vessel occlusion

Intrinsic (may require biopsy for diagnosis)

luminal : stones, clots, sloughed papillaemural: malignancy, BPH, urethral stricturesextrinsic compression: malignancy, retroperitoneal fibrosis

Post-renal - UT obstruction


15/18


8. Investigations


16/18


CLINICAL PRESENTATION One of many renal factors involved in the genesis of HPT is the total number of nephrons in the

kidney.

Renal artery stenosis (RAS) is an important cause of 2 HPT. 23% of malignant HPT is the result ofrenovascular causes. Aetiology of RAS

Artherosclerosis Polyartheristis nodosa Radiation-induced Takayasus arteritis

Haemodynamic effects of RAS are; 1) reduction of bloodflow, 2) decreased perfusion pressure 3) activation ofpressor mechanisms.

RAS is caused by one of two pathological entities Fibromascular disease

10-25% of all RAS, young female (15-40 yo) Medial diseae 90%, often involves distal RA

Atherosclerotic renovascular disease (ARVD) Incidence increases with age In most pts the atherosclerotic lesion is ostial (within 1cm of the origin of the RA) and

usually associated with SYMPTOMATIC atherosclerotic vascular disease elsewhere.

Signs and symptoms

- HPT (presents in 50%) but bear in mind, not all pts with RAS are HPT as a result.- Progressive HPT in a pt with previously stable HPT.


17/18


- Sodium retention (ankle and pulmonary oedema)- Proteinuria (usually sub-nephrotic range)- Decreased GFR- vascular sclerosis- tubular atrophy- interstitial fibrosis with inflammatory cellular infiltrate atubular glomeruli- cholesterol emboli- secondary focal segmental glomerulosclerosis (FSGS)

Investigation SCr, eGFR, U&E Urine dipstick, uPCR or uACR Evidence of vascular disease e.g.. ECG difference of >1.5cm in renal length in USS kidneys CT angiography MRA Formal angiography

RESULTS Patients with abdominal audible bruits, as well as bruits over carotid arteries suggestive of generalized

arterial disease Doppler ultrasonography showing >1.5 cm renal asymmetry, Recurrent flash pulmonary oedema without cardiopulmonary disease Progressive chronic renal failure in patients with evidence of generalized atherosclerosis.

Predictors of Kidney salvageability1. Kidney size > 9 cm2. Resistive index < 0.803. Recent increase in serum creatinine4. Decrease in GFR during ACE inhibition5. Absence of glomerular or interstitial fibrosis on kidney biopsy

Imaging1. MRA gold standard2. Radionuclide studies screening

3. Doppler -4. Helical (spiral) CT scanning

Consider referral1. eGFR10mL/min in 5 years). Microscopic haematuria. Proteinuria ( uACR >70mg/mmol, uPCR >100mg/mmol ) unless known to be due to

diabetes and appropriately treated. > 15% decline in eGFR with commencement of an ACE-I or ARB (? renovascular disease). Suspected systemic illness (e.g. SLE, myeloma).


18/18


Hb 150/90 despite three antihypertensive agents).

3. eGFR >60mL/min and other evidence of renal disease/damage: Urine Albumin-to-Creatinine Ratio ( uACR) >70 or uPCR >100mg/mmol. uACR >30 or uPCR >50mg/mmol and microscopic haematuria. Abnormal renal imaging, e.g. renal cysts.

4. Other indications:Suspected acute kidney injury.

MANAGEMENTFor all stages

Non-pharmacological Pharmacological1. Exclude AKI.2. Explanation, education, and reassurance

regarding the causes and consequences ofCKD.

3. Smoking cessation.4. Weight reduction if obese.5. Encourage aerobic exercise.

1. Aspirin 75mg, according to 10-year CV riskestimate.

2. Treat lipids, according to best practiceguidelines.

3. Avoid NSAIDs and other nephrotoxic drugs.4. Limit alcohol to HPT

In renal artery stenosis, renal perfusion pressure is reduced and nephron transit time is prolonged onthe side of the stenosis; salt and water reabsorption is therefore increased.

Urine from the ischaemic kidney is more concentrated and has a lower sodium concentration thanurine from the contralateral kidney.

Creatinine clearance is decreased on the ischaemic side.

Themed Week 8 - Renal

Documents

Transcript of Themed Week 8 - Renal