nephrology notes 2015

8/18/2019 Nephrology Notes 2015

1/81

Renal anatomyThe tables b elow show the anatomical relations o f the kidneys:

Right kidney

Direct contact Layer of peritoneum in-between

Right suprarenal glandDuodenumColon

Liver Distal part of small intestine

Left kidney

Direct contact Layer of peritoneum in-between

Left suprarenal glandPancreasColon

StomachSpleenDistal part of small intestine

Renal physiology• Renal blood ow is 20 -25% of cardiac ou tput• Renal cortical blood ow > medullary blood ow so, tubular cells m ore prone to ischaemia

1


2/81

Acute kidney injuryAcute tubular necrosis vs. prerenal uraemiaPrerenal uraemia - kidneys hold on to sodium to preserve volume

Pre-renal uraemia Acute tubular necrosis

Urine sodium < 20 mmol/L > 30 mmol/L

ractional sodium e!cretion" < #$ > #$

ractional urea e!cretion"" < 3%$ >3%$

Urine&plasma osmolality > #'% < #'#

Urine&plasma urea > #0 < (

)pecific *ra+ity > #020 < #0#0

Urine ,bland, sediment brown *ranular casts

esponse to fluid c.allen*e es o

*fractional sodium excretion = (urine sodium/plasma sodium) / (urine creatinine/plasmacreatinine) x 1 00

**fractional urea excretion = (urine urea /blood urea) / (urine creatinine/plasma creatinine) x 1 00In acute tubular necrosis (ATN) urine to plasma osmolality should be less than 1.1urinary sodium e!cretion is typically more than "# mmol$% and urinary urea e!cretionless than 1"# mmol$%.

I& this patient had a physiological oliguria there 'ould still be preservation o& urineconcentration 'ith lo' urinary sodium.

oth ATN and pre renal &ailure can present 'ith a &all in urine output. There is such amarked variation in urine urea concentration that it is seldom used as a clinicalguide.

*apillary necrosisCauses

• chronic a nalgesia use• sickle cell disease

+


3/81

• TB• acute pyelonephritis• diabetes mellitus

Features• fever, loin pain, haematuria• IVU - papillary necrosis with renal scarring - 'cup & spill'

Nephroto!icity due to contrast mediaContrast media nephrotoxicity may b e d ened as a 25% increase in creatinine occurring within

3 days of the intravascular administration of contrast media.

Risk factors include

• known renal impairment (especially diabetic n ephropathy)• age > 70 years• dehydration• cardiac failure• the use o f nephrotoxic drugs su ch a s NSAIDs

Prevention

• the evidence base currently s upports t he use of intravenous 0.9% NaCl a t a rate of 1

mL/kg/hour for 12 hours p re- and post - procedure. There is a lso evidence to support the

use of isotonic sodium bicarbonate• N-acetylcysteine (usually g iven orally ) has b een shown to reduce the incidence of

contrast-nephropathy in some studies b ut the evidence base is n ot as st rong as f or uid

therapy

,


4/81

-% renal complicationsWHO classication

• class I: normal kidney• class II: mesangial glomerulonephritis• class III: focal (and segmental) proliferative glomerulonephritis• class I V: diffuse proliferative glomerulonephritis• class V : diffuse membranous g lomerulonephritis• class VI: sclerosing glomerulonephritis

Class IV (diffuse proliferative glomerulonephritis) is t he most common and severe form. Renal

biopsy characteristically shows the following ndings:

• glomeruli shows endothelial and mesangial proliferation , 'wire-loop' appearance• if severe, the capillary wall may be thickened se condary to immune complex d eposition• electron microscopy sh ows subendothelial immune com plex deposits• granular a ppearance o n immunouorescence

/


5/81

Diffuse proliferative SLE. Proliferation of endothelial and mesangial cells. The thickening of the capillary w all

results in a 'wire-loop' ap pearance. Some cr escents ar e p resent.

Management

• treat hypertension• corticosteroids if clinical evidence of disease• immunosuppressants e.g. aza thiopine/cyclophosphamide

%upus nephritis• Histologically, a number of different types of renal disease are recognised in SLE, with

immune-complex m ediated glomerular disease being the most common.• The up to date International Society o f Nephrology/Renal Pathology S ociety 2003

classication divides these into six different patterns: I - minimal mesangial

II - mesangial proliferative III - focal IV - diffuse V - membranous VI - advanced sclerosis

0


6/81

I - minimal mesangial:• Light microscopy Glomeruli appear normal, but• Immunouorescence de monstrates m esangial immune deposits.

II - Mesangial proliferative nephritis • Presents clinically as microscopic haematuria and/or proteinuria.• Hypertension is incommon and nephrotic syn drome a nd renal impairment are ve ry rarely

seen.• Biopsy d emonstrates:

Segmental areas o f increased mesangial matrix a nd cellularity, with m esangial immune

deposits.

A few isolated subepithelial or subendothelial deposits m ay b e visible by

immunouorescence.

• The prognosis is good a nd specic treatment is o nly indicated if the disease progresses.

III - Focal disease:• More advanced, but still affects < 50% of glomeruli .• Haematuria a nd p roteinuria is a lmost always s een• nephrotic syn drome, hypertension and elevated c reatinine may be present.• Biopsy demonstrates:

Active or inactive focal , segmental or global endo- or extracapillary glomerulonephritisinvolving < 50% of glomeruli,

typically with focal subendothelial immune deposits ,

with or without mesangial alterations It is further subdivided:

A: Active lesions: focal proliferative lupus nephritis

A/C: Active and chronic lesions: focal proliferative and sclerosing lupus nephritis

C: Chronic inactive lesions w ith glomerular scars: focal sclerosing lupus n ephritis• Prognosis is variable.

IV - Diffuse glomerulonephritis:• The most common and severe form of lupus nephritis.• Haematuria and proteinuria are almost always present, and

"


7/81

• nephrotic syn drome, hypertension and renal impairment common.• Biopsies d emonstrate

Active or inactive diffuse , segmental or global endo- or extracapillary glomerulonephritis

involving > 50% of all glomeruli,

typically with diffuse su bendothelial immune deposits ,

with or without mesangial alterations This class is divided into:

Diffuse segmental (IV-S) when more than 50% of the involved glomeruli have

segmental lesions, and

Diffuse global (IV-G) when more t han 50% of involved glomeruli have global lesions.

(Segmental is d ened as a glomerular lesions t hat involves l ess than half of the glomerular

tuft)

IV-S (A): Active lesions, diffuse segmental proliferative lupus nephritis

IV-G (A): Active lesions, diffuse global proliferativeIV-S (A/C): Active and chronic lesions, diffuse segmental proliferative and sclerosing lupus

nephritis

IV-S (C): Chronic i nactive lesions w ith scars, diffuse segmental sclerosing lupus n ephritis

IV-G (C): Chronic inactive lesions with scars: diffuse global sclerosing lupus nephritis• Immunosuppressive therapy is r equired in these cases t o prevent progressive to end-stage

renal failure.

V - Membranous lupus nephritis:• Patients w ith membranous lupus n ephritis t end to present with nephrotic syn drome.• Microscopic h aematuria and hypertension may a lso be seen.• Biopsies show

Global or segmental subepithelial immune deposits or their morphologic s equelae,

with or without mesangial alterations• It may o ccur in combination with class III or IV, in which case both are diagnosed.• Progression is va riable, and immunosuppression is n ot always needed.

VI - advanced sclerosis: >90% of glomeruli are globally s clerosed without residual activity.

With regard to the management of lupus n ephritis a biopsy is i ndicated in those patients w ith

abnormal urinalysis a nd/or reduced renal function.


8/81

This can provide a histological classication as well as information regarding activity,

chronicity and prognosis.

Cyclophosphamide , mycophenolate m ofetil and azathioprine reduce mortality in

proliferative forms of lupus glomerulonephritis.

RhabdomyolysisRhabdomyolysis w ill typically feature in the exam as a patient who has h ad a fall or prolonged

epileptic s eizure and is f ound to have acute renal failure on admission

Features

• acute renal failure with disproportionately rai sed creatinine

• elevated CK• myoglobinuria• hypocalcaemia (myoglobin binds cal cium)• elevated phosphate (released from myocytes)

Causes

• seizure• collapse/coma (e.g. elderly patients collapses at home, found 8 hours later)• ecstasy (MDMA)• crush injury• McArdle's syndr ome• drugs: st atins

Management

• IV uids t o maintain good urine output• urinary alkalinization is s ometimes u sed

2


9/81

Acute vs. chronic renal &ailureBest way to differentiate is r enal ultrasound, most patients w ith CRF have bilateral small

kidneys

Exceptions

• autosomal dominant polycystic kidney d isease ADPCK• diabetic nephropathy• amyloidosis• HIV-associated nephropathy

Other features suggesting CRF rather than ARF

• hypocalcaemia (due to lack o f vitamin D)

3hronic kidney disease causesCommon causes of chronic kidney disease

• diabetic nephropathy• chronic glomerulonephritis• chronic pyelonephritis• hypertension• adult polycystic kidney disease

4


10/81

3hronic kidney disease5 e67R and classi8cationSerum creatinine may not provide an accurate estimate of renal function due to differences i n

muscle. For this r eason formulas w ere develop to help estimate the glomerular ltration rate

(estimated GFR or eGFR). The most commonly use d formula is the Modication of Diet in Renal

Disease ( MDRD ) equation, which uses t he following variables:

serum creatinine age gender ethnicity

Factors w hich may a ffect the result

pregnancy• muscle mass (e.g. amputees, body-builders)• eating red meat 12 hours prior to the sample being taken

CKD may be cl assied according to GFR:

1 D sta*e ran*e

1 > 40 ml/min , with some sign of 5idney dama*e on other tests (if all the kidney testsare normal, there is no C!D"

# 60-40 ml/min with some sign of 5idney dama*e (if kidney tests are normal, there is noC!D"

$a 7%-%4 ml/min, a moderate reduction in kidney function

$% 30-77 ml/min , a moderate reduction in kidney function

& #%-24 ml/min, a severe reduction in kidney function

' < #% ml/min, esta%lished kidney failure dialysis or a kidney transplant may %e needed

*i.e. normal U&Es a nd no proteinuria

Anaemia in 3hronic kidney disease

1#


11/81

• Patients w ith chronic ki dney disease (CKD) may develop anaemia due to a variety o f factors,

the most signicant of which is r educed erythropoietin levels. This i s usually a normochromic

normocytic ana emia a nd becomes ap parent when the GFR is less t han 35 ml/min (other

causes of anaemia should be considered if the GFR is > 60 ml/min).• Anaemia in CKD predisposes t o the development of LVH - associated with a threefold

increase in mortality in renal patients

Causes o f anaemia in renal failure:• reduced erythropoietin levels - the most signicant factor• reduced erythropoiesis due to toxic effects of uraemia on bone marrow• reduced absorption of iron• anorexia/nausea due to uraemia• reduced red cell survival (especially in haemodialysis)

• blood loss due to capillary fragility and poor platelet function• stress ulceration leading to chronic b lood loss

Management:• the 2 011 NICE guidelines su ggest a target haemoglobin o f 10 - 12 g/dl• determination and optimisation of iron status should be carried out prior to the

administration of erythropoiesis-stimulating agents (ESA)• Many patients, especially those on haemodialysis, will require IV iron• ESAs su ch as e rythropoietin and darbepoetin should be used in those 'who are likely to

benet in terms of quality of life and physical function'

rythropoietinErythropoietin is a haematopoietic growth factor that stimulates the production of erythrocytes.

The main uses o f erythropoietin are to treat the anaemia associated with CKD a nd that

associated with cytotoxic therapy .

Side-effects o f erythropoietin

• accelerated hypertension p otentially leading to encephalopathy and seizures (blood

pressure increases in 25% o f patients) bone aches u-like symptoms

11


12/81

skin ras hes, urticaria (pruritus o f Hyperviscosity Syndrome )• pure red cell aplasia (due to antibodies a gainst erythropoietin)

The risk is g reatly r educed with darbepoetin (Aranesp)• raised PCV increases r isk of thrombosis (e.g. Fistula)• iron deciency 2 nd to increased erythropoiesis

There are a number of reasons w hy p atients m ay fail to respond to erythropoietin therapy:

• iron deciency• inadequate dose• concurrent infection/inammation (MIA)• hyperparathyroid bone disease• aluminium toxicity

Due to the mild chronic inammatory n ature of chronic renal disease a ferritin


13/81

• Aplastic a nemia,• bone marrow suppression• Sideroblastic a nemias• Ineffective erythropoiesis• Liver disease with reduced transferrin synthesis, and• Monoclonal immunoglobulin with antitransferrin activity (rare).

It is r ecommended that patients w ith anaemia secondary to chronic renal failure should

have:• a ferritin level maintained at 200-500 μg/L and either• transferrin saturations >20% or• percentage hypochromic red cells < 6%

• Where patients h ave absolute iron deciency oral iron supplementation may be adequate.

However where there is functional iron deciency, intravenous iron replacement is

recommended.

• Blood transfusion may b e indicated where there are severe symptoms o f anaemia or a

particularly low haemoglobin level.• Where possible blood transfusion should be avoided in patients w ho may b e candidates

for transplantation as t he development of antibodies t o alloantigens m ay make future

transplantation more problematic.

• Erythropoietin should be commenced when anaemia has reached a level requiring

treatment and usually o nly a fter the patient has h ad their iron stores a dequately replaced.

1,


14/81

3hronic kidney disease5 hypertension• The majority o f patients w ith chronic k idney d isease (CKD) will require more than two drugs

to treat hypertension.• ACE inhibitors are rst line a nd are particularly helpful in proteinuric renal disease (e.g.

diabetic n ephropathy). As t hese drugs t end to reduce ltration pressure a small fall in

glomerular ltration pressure (GFR) and rise in creatinine can be expected. NICE suggest that

a d ecrease in eGFR of up to 25% o r a rise in creatinine of up to 30% is acceptable ,

although any rise should prompt careful monitoring and exclusion of other causes ( e.g.

NSAIDs). A rise greater than this m ay indicate underlying renovascular d isease

• Furosemide is u seful as a anti-hypertensive in patients w ith CKD, particularly when the GFR

falls to below 45 ml/min *. It has t he added benet of lowering serum potassium . High

doses a re usually required. If the patient becomes a t risk of dehydration (e.g. Gastroenteritis)

then consideration should be given to temporarily stopping the drug

*the NKF K/DOQI guidelines suggest a lower cut-off of less t han 30 ml/min

1/


15/81

*roteinuria• Proteinuria is an important marker of chronic kidney disease, especially for diabetic

nephropathy.• NICE recommend using albumin: creatinine ratio in preference to protein: creatinine

ratio (PCR) when identifying p atients with proteinuria as it has greater sensitivity .• For quantication and monitoring of proteinuria, PCR can be used as a n alternative, although

ACR is r ecommended in diabetics.• Urine reagent strips a re not recommended unless t hey e xpress t he result as a n ACR

Approximate e quivalent values

A1 8m*/mmol9 P1 8m*/mmol9 Urinary protein e!cretion 8*/27 .9

30 %0 0'%

:0 #00 #

Collecting an ACR sample

•

by c ollecting a 'spot' sample it avoids t he need to collect urine over a 24 hour period inorder to detect or quantify proteinuria

• should be a rst-pass m orning u rine specimen• if the initial ACR is > 30 mg/mmol and < 70 mg/mmol , conrm by a subsequent early

morning sample. If the initial ACR is > 70 mg/mmol a repeat sample need not be tested

10


16/81

Interpreting the ACR results

• in non-diabetics an ACR > 30 mg/mmol is considered clinically signicant proteinuria• in diabetics microalbuminuria (ACR > 2.5 mg/mmol in men and ACR > 3.5 mg/mmol in

women) is co nsidered clinically si gnicant

BP targets

CKD with proteinuria ACR ≥70 mg/mmol or d iabetes ---- blood pressure target < 130/80 mmHg .

The NICE guidelines r ecommend that a b lood pressure t arget < 140/90 mmHg sh ould be used innon-diabetic pa tients with CKD and an ACR


17/81

• Addison's• rhabdomyolysis• massive blood transfusion

Foods t hat are h igh in potassium:

• salt substitutes ( i.e. Contain potassium rather than sodium)• bananas, oranges, kiwi fruit, avocado, spinach, tomatoes

*beta-blockers interfere with potassium transport into cells and can potentially causehyperkalaemia in renal failure patients - remember beta-agonists, e.g. Salbutamol, aresometimes u sed a s em ergency treatment

**both unfractionated and LMWH ca n ca use h yperkalaemia. This is thought to be c aused byinhibition of aldosterone s ecretion

Management: may b e categorized by the aims o f treatment

Stabilization of the c ardiac membrane• intravenous calcium gluconate

Short-term shift in potassium from ECF to ICF compartment• combined insulin/dextrose infusion• nebulised sal butamol

Removal of potassium from the body• calcium resonium (orally o r enema)• loop diuretics• dialysis

The initiation of emergency renal replacement therapy is u sually required for:1) Acute life threatening hyperkalaemia which is resistant to treatment2) Development of metabolic a cidosis w hich is n on-responsive to uid.3) Development of uid overload, which may m anifest itself as p ulmonary oe dema.4) Development of uraemia which may manifest itself as pericarditis, neuropathy and

confusional state.

1


18/81

Primary h yperparathyroidism is a ssociated with hypercalcaemia and an inappropriately

raised parathyroid hormone, the phosphate level is typically low.

Secondary hyperparathyroidism is a ssociated with hypocalcaemia and an appropriately

elevated parathyroid hormone level, the phosphate level is va riable depending upon theaetiology (high in renal failure, low in vitamin D deciency).

Hypercalaemia o f malignancy and iatrogenic h ypercalcaemia would both be as sociated

with a high calcium and low parathyroid hormone level.

12


19/81

Acid ase alanceThe anion gap is a simple method for discerning causes o f metabolic a cidosis.It relies on the fact that the concentration of cations in plasma must equal the

concentration of anions.Cations h ave positive charge, anions h ave negative charge.

[Cations] = [Anions]

Most ions a re unmeasured and individually have a low concentration.The measured ions i n sufficient concentration are sodium, potassium, chloride and

bicarbonate. Therefore:

[Na] + [K] + [unmeasured cations] = [Cl] + [HCO3] [unmeasured anions]

And rearranging:

([Na] + [K]) - ([Cl] + [HCO3]) = [unmeasured anions] - [unmeasured cations].

The anion gap is the difference b etween unmeasured anions a nd unmeasured cationsIn health is b etween 10-18 mmol/l.This v alue is h elpful in discerning causes o f metabolic a cidosis,⇒ As i f it is r aised the acidosis i s d ue to an unmeasured ion - such as l actate, ketones,

salicylate in lactic a cidosis, diabetic ketoacidosis and aspirin overdose respectively, and

methanol or ethylene glycol poisoning

⇒ A normal anion gap suggests a n acidosis d ue to bicarbonate or chloride handling -

such as r enal tubular acidosis, diarrhoea, pancreatic stula, ammonium chloride

ingestion or acetazolamide.

14


20/81

A metabolic a lkalosis may b e seen in vomiting, from other diuretics o r excessive

bicarbonate or antacid therapy.

Respiratory acidosis is d ened by a raised pCO2 and is t ypically related to type 2

respiratory failure. It is se en in severe COPD, asthma, pneumonia or pulmonary oedema

and hypoventilation due to sedatives, muscular disease (for example, myasthenia gravis)or chest wall trauma.

Respiratory alkalosis is s een in any cause of hyperventilation, either due to anxiety, or in

hypoxic st ates su ch as a sthma where adequate ventilation is p reserved.

• Carbonic anhydrase ca talyses t he rst part of the reversible reaction in which carbon

dioxide and water are converted to carbonic a cid (and vice versa):

CO2 + H2O ←→ H+ + HCO3-

• In the kidney, carbonic anhydrase is found in the proximal convoluted tubule.

• The equation is n ormally s hifted to the left allowing the formed carbon dioxide to diffuse

back into the systemic c irculation.

• In the presence of a carbonic a nhydrase inhibitor, such as acetazolamide , the equation is

shifted to the r ight and more H+ and HCO3- is p roduced.• The H+ is r eabsorbed alongside chloride ions. However, the bicarbonate is p assed in the

urine as it is not easily absorbed in the nephron.• This results in a hyperchloraemic, normal anion gap m etabolic acidosis .

This e ffect can be used therapeutically to prevent acute mountain sickness . Whereasnormally t he hypoxic h igh altitude would stimulate ventilation resulting in a respiratory

alkalosis, acetazolamide use causes net renal excretion of bicarbonate, correcting this

abnormality.

+#


21/81

With respiratory alkalosis t he kidneys would physiologically excrete bicarbonate, but this

takes t wo to three days. Acetazolamide speeds t his p rocess.

Causes of respiratory alkalosis:

• Central causes - stroke, meningitis, CNS tumour

• Drugs - salicylates

• Anxiety

• Pregnancy.

Causes of metabolic alkalosis:

• Vomiting - anorexia ner osa, gastric outlet obstruction

• !ngestion of base

• Prolonge" #ypokalaemia of any cause - t#e ki"ney allo$s %& to be lost in an effortto retain '&. Diuretic t#erapy is a common example.

• (urns.

Renal tubular acidosisAll three types o f renal tubular acidosis ( RTA) are associated with hyperchloraemic metabolic

acidosis (normal anion gap)

Type 1 RTA (distal)• inability to generate acid urine (secrete H+) in distal tubule• causes hypokalaemia• complications include nephrocalcinosis and renal stones• causes include idiopathic, RA, SLE, Sjogren's

+1


22/81

Abdominal x-ray showing nephrocalcinosis - a cl assical nding in type 1 RTA

Type 2 R TA (proximal)• decreased HCO3- reabsorption in proximal tubule• causes hypoka laemia• complications include osteomalacia causes include:

1) idiopathic,2) as p art of Fanconi syndrome ,3) Wilson's d isease ,4) cystinosis ,5) outdated tetracyclines

Type 4 R TA ( hyperkalaemic ) hyporeninenimic h ypoaldosteronimic• reduction in aldosterone leads i n turn to a reduction in proximal tubular ammonium

excretion• causes hype rkalaemia• causes include hypoaldosteronism, diabetes

Fanconi syndromeFanconi syndrome describes a generalised disorder of renal tubular transport resulting in:

• type 2 (proximal) renal tubular acidosis• aminoaciduria• glycosuria

++


23/81

• phosphaturia• osteomalacia

Causes• cystinosis ( most common cause in children)• Sjogren's syn drome• Wilson's d isease• multiple myeloma• nephrotic syndrome

Diabetic nephropathy

+,


24/81

• commonest cause o f end-stage renal disease ( ESRD) in the western world• 33% of patients w ith type 1 diabetes m ellitus h ave diabetic n ephropathy by the age of 40

years• approximately 5-10% of patients w ith type 1 d iabetes m ellitus d evelop (ESRD)

The pathophysiology is p oorly u nderstood, however:• changes to the haemodynamics of the glomerulus i s t hought to be key, which leads t o an

increased glomerular capillary pressure• Histological changes i nclude:

⇒ BM thickening ,⇒ capillary obliteration ,⇒ mesangial widening .⇒

Nodulular hyaline a reas d evelop in the glomuli - Kimmelstiel-Wilson nodules

Thickening of the basement membrane is se en alongside multiple Kimmelstiel-Wilson nodules

Severe arteriolosclerosis i s s een in the afferent arteriole on the left of the slide.

Multiple, smaller acellular nodules a re seen in the glomerulus - Kimmelstiel-Wilson nodules.

The tubular basement membrane is al so thickened

+/


25/81

Risk factors for developing diabetic nephropathy

;odifiable on-modifiable

)ypertension)yperlipidaemiaSmokingPoor glycaemic controlRaised dietary protein

*ale se+Duration of dia%etes

enetic predisposition (e-g- .C/ gene polymorphisms"

Stages of Diabetic nephropathy:Diabetic n ephropathy may b e c lassied a s o ccurring in ve s tages*:

Stage 1• hyperltration: increase in GFR• may be reversible

Stage 2 (silent or latent phase)• most patients d o not develop microalbuminuria for 10 years

GFR remains elevated

Stage 3 ( incipient nephropathy)• microalbuminuria (albumin excretion of 30-300 mg/day , dipstick negative )( ACR >2.5 )

Stage 4 ( overt nephropathy)• persistent proteinuria (albumin excretion > 300 mg/day , dipstick positive )• hypertension is present in most patients• histology sh ows diffuse glomerulosclerosis and focal glomerulosclerosis (Kimmelstiel-

Wilson nodules)

Stage 5• ESRD , GFR typically < 10ml/min• RRT needed

+0


26/81

The timeline given here is f or type 1 diabetics. Patients w ith type 2 diabetes m ellitus ( T2DM)

progress t hrough similar stages b ut in a different timescale - some T2DM patients m ay progress

quickly t o the later stages

ARPKD• Autosomal recessive polycystic kidney disease ( ARPKD) is much less com mon than

autosomal dominant disease (ADPKD).It is d ue to a defect in a gene located on chromosome 6

Diagnosis may be m ade on prenatal ultrasound o r in early infancy with abdominal masses

and renal failure.Newborns m ay a lso have features co nsistent with Potter's syn drome se condary to

oligohydramnios .ESRD develops i n childhood.Patients also typically have liver involvement , for example portal and interlobular brosis .Renal biopsy typically shows multiple cylindrical lesions a t right angles to cortical surface.

Autosomal dominant polycystic kidney d isease (ADPKD)

• The most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians.• Two disease loci have been identied, PKD1 and PKD2, which code for polycystin-1 and

polycystin-2 respectively

ADP D type # ADP D type 2

0' of cases 1' of cases

Chromosome 12 Chromosome &

Presents with renal failure earlier

+"


27/81

• The screening investigation for relatives i s abdominal ultrasound (start at 18 years)• Formal screening for AKPD occurs i n early a dulthood, usually w ith a renal ultrasound scan.• Its sensitivity approaches 100% in those over 30 years , but falls to less than 70% under this

age.

Ultrasound diagnostic c riteria (in patients with positive family h istory )• two cysts, unilateral or bilateral, if aged < 30 years• two cysts i n both kidneys i f aged 30-59 years• four cysts i n both kidneys i f aged > 60 years

Features• hypertension• recurrent UTIs•

abdominal pain• renal stones• haematuria• chronic kidney disease

Extra-renal manifestations• Liver cysts ( 70%)• Berry aneurysms (8%)• cardiovascular system:

mitral valve prolapse,mitral/tricuspid incompetence,aortic root dilation, aortic dissection

• cysts i n other organs: pancreas, spleen; very rarely: thyroid, oesophagus, ovary

9n average patients progress to end stage renal &ailure bet'een the ageso& /# and "# years.In these patients the renal &unction usually deteriorates in a gradual&ashion usually 'ith a drop in creatinine clearance o& 0$" ml$min$year (atleast 1# years &or this patient or possibly sooner i& * not ade:uatelymanaged).

Treatment should include a high ;uid intake (to prevent the &ormation o&renal stones or blood clots) and regular &ollo' up o& blood pressure andrenal &unction. %oin pain should be treated symptomatically and

+


28/81

hypertension should be managed 'ith standard antihypertensivemedications.


29/81

CT showing multiple cysts o f varying sizes i n the liver, and bilateral kidneys with little remaining normal renal

parenchyma.

+4


30/81

Haematuria• The management of patients w ith haematuria is o ften difficult due to the absence of widely

followed guidelines.• It is s ometimes unclear whether patients a re best managed in primary c are, by u rologists o r

by nephrologists.• The terminology su rrounding haematuria is ch anging.• Microscopic o r dipstick positive haematuria is i ncreasingly t ermed non-visible haematuria• whilst macroscopic haematuria is termed visible haematuria • Non-visible haematuria is found in around 2.5% of the population.

Causes o f transient or spurious n on-visible h aematuria• UTI

• menstruation• sexual intercourse• vigorous e xercise (this n ormally s ettles a fter around 3 days)

Spurious ca uses - red/orange urine, where blood is n ot present on dipstick• foods: beetroot, rhubarb• drugs: rifampicin, doxorubicin, Metronidazole

Causes o f persistent non-visible haematuria

1) cancer (bladder, renal, prostate)

2) stones

3) benign prostatic hyperplasia

4) prostatitis

5) urethritis e.g. Chlamydia

6) renal causes: IgA nephropathy, thin basement membrane d isease

Management:

Current evidence does n ot support screening for haematuria.The incidence of non-visible haematuria is similar in patients taking aspirin/warfarin to the

general population hence these patients sh ould also be investigated.

,#


31/81

Testing

1)urine dipstick is the test of choice for detecting haematuria⇒ persistent non-visible haematuria is o ften dened as b lood being present in 2 out of 3

samples t ested 2-3 weeks ap art

2) BP , RFTs, and albumin:creatinine (ACR) or protein:creatinine ratio (PCR) should also be

checked

3)urine microscopy may b e u sed but time to a nalysis si gnicantly affects the n umber of RBCs

detected

NICE urgent cancer referral guidelines1) of any age with painless macroscopic haematuria

2) patients under the age of 40 ye ars w ith normal renal function, no proteinuria and who are

normotensive d o not need to be referred and may b e managed in primary car e

3) aged 40 years and older who present with recurrent or persistent UTI a ssociated with

haematuria

4) aged 50 years an d older who are found to have unexplained micr oscopic haematuria

,1


32/81

Alport's syndrome• Usually inherited in an X-linked dominant pattern*.• It is d ue to a defect in the gene which codes f or type IV collagen resulting in an abnormal

glomerular-basement membrane ( GBM ).• The disease i s m ore severe in males• females rarely developing renal failure• Patients w ith Alport syndrome are at risk of developing antiglomerular basement

membrane disease (Goodpasture's d isease) following transplantation, as t heir immune

systems h ave never been exposed to type IV collagen and hence lack tolerance.• Favourite question is a n Alport's patient with a failing renal transplant . This m ay be

caused by presence of anti-GBM antibodies leading to Goodpasture's syndrome like

picture• Alport's s yndrome usually p resents i n childhood .• Type IV collagen is found in the basement membrane of the kidney, inner ear and eye, so

therefore extra-renal manifestations i nclude bilateral sensorineural deafness and ocular

abnormalities su ch as co rneal dystrophies a nd lens a bnormalities.

The following features m ay be se en:• microscopic and macroscopic haematuria with or without proteinuria• progressive renal failure bilateral sensorineural deafness• lenticonus : protrusion of the lens s urface into the anterior chamber retinitis p igmentosa• renal biopsy: splitting of lamina d ensa seen on EM

,+


33/81

The disease is X-linked dominant in 85% of cases 10-15% of cases a re inherited in a n a utosomal recessive fashion with rare autosomal

dominant variants existingthe m ost common genetic ab normality is a m utation in the C OL4A5 gene (involved in type

IV collagen synthesis) on the X chromosome

COL4A3 and COL4A4 (genes also involved in type IV collagen synthesis) are located onchromosome 2, explaining why this d isease may also have autosomal recessive or

dominant inheritance. As Alport syndrome is X linked in 85% of cases. Therefore, as o nly the Y

chromosome is p assed from father to son there is n o chance o f the so n having the

disease from only affected father

lomerulonephritidesKnowing a few key facts i s t he best way to approach the difficult subject of glomerulonephritis:

Minimal change disease• Typically a child with nephrotic syndrome (accounts for 80%)• causes: Hodgkin's, NSAIDs• good response to s teroids

Membranous glomerulonephritis• presentation: proteinuria / nephrotic s yndrome / chronic k idney d isease• cause: infections, rheumatoid drugs, malignancy• 1/3 resolve, 1/3 respond to cytotoxics, 1/3 develop chronic kidney disease

Focal segmental glomerulosclerosis• may be idiopathic o r secondary to HIV, heroin• presentation: proteinuria / nephrotic s yndrome / chronic k idney d isease

,,


34/81

IgA nephropathy - aka Berger's disease, mesangioproliferative GN• typically yo ung adult with haematuria following an URTI

Diffuse proliferative glomerulonephritis• classical post-streptococcal glomerulonephritis i n child• presents a s n ephritic s yndrome / acute kidney injury• most common form of renal disease in SLE

Rapidly progressive glomerulonephritis - aka crescentic glomerulonephritis• rapid onset, often presenting as a cute kidney injury• causes include Goodpasture's, ANCA positive vasculitis

Mesangiocapillary g lomerulonephritis (membranoproliferative)• type 1: cryoglobulinaemia, hepatitis C• type 2: partial lipodystrophy

lomerulonephritis and lo! complement1) post-streptococcal glomerulonephritis

2) subacute bacterial endocarditis

3) systemic lupus er ythematosus

4) mesangiocapillary glomerulonephritis

"ephrotic syndromeTriad of:1) Proteinuria (> 3g/24hr) causing

2) Hypoalbuminaemia (< 30g/L) and

3) Oedema

Loss of antithrombin-III, proteins C and S and an associated rise in brinogen levels

predispose to thrombosis.

,/


35/81

Loss o f thyroxine-binding globulin lowers t he total, but not free, thyroxine levels.

"ephrotic syndrome complications:

• increased risk of infection due to urinary immunoglobulin loss•

increased risk of thromboembolism related to loss of antithrombin III and plasminogen inthe urine

• hyperlipidaemia• hypocalcaemia (vitamin D and binding protein lost in urine)• acute renal failure

,0


36/81

#inimal change disease• Always p resents a s ne phrotic syn drome, accounting for 75% of cases in children a nd 25% in

adults.• The majority o f cases a re idiopathic, but in around 10-20% a cause is found:

1) drugs: NSAIDs, rifampicin

2) Hodgkin's lymphoma, thymoma

3) infectious mononucleosis

Pathophysiology• T-cell and cytokine mediated damage to the GBM → polyanion loss• the resultant reduction of electrostatic charge → increased glomerular permeability to

serum albumin

Features• nephrotic syndrome• normotension - hypertension is r are• highly s elective p roteinuria : only intermediate-sized proteins su ch as a lbumin and

transferrin leak through the glomerulus

• renal biopsy: electron microscopy shows f usion of podocytesManagement

• majority o f cases ( 80%) are steroid responsive• cyclophosphamide is the next step for steroid resistant cases

Prognosis i s o verall good, although relapse is c ommon. Roughly:• 1/3 have just one ep isode• 1/3 have infrequent relapses• 1/3 have frequent relapses w hich stop before adulthood

,"


37/81

#embranous glomerulonephritis The commonest type of glomerulonephritis in adults

The third most common cause o f ESRF.

It usually p resents w ith nephrotic s yndrome or proteinuria.

Renal biopsy de monstrates:• EM : the basement membrane is thickened with subepithelial electron dense deposits .

This c reates a 'spike and dome' appearance

Causes

1) idiopathic

2) infections: hepatitis B, malaria, syphilis3) malignancy: lung cancer, lymphoma, leukaemia

4) drugs: gold, penicillamine, NSAIDs

5) autoimmune diseases: systemic lupus e rythematosus ( class V disease), thyroiditis,

rheumatoid

Prognosis - rule of thirds• one-third: spontaneous remission• one-third: remain proteinuric (r espond to cytotoxics)• one-third: develop ESRF

Good prognostic features include:

1)female s ex,2)young a ge at presentation and

,


38/81

3)asymptomatic4)proteinuria of a modest degree a t the time of presentation

Management

1) Immunosuppression:

A combination of corticosteroid + another agent such as chlorambucil is o ften usedcorticosteroids a lone have not been shown to be effective

2) blood pressure control: ACE inhibitors have been shown to reduce proteinuria

3) consider anticoagulation

Silver-stained sect ion showing thickened basement membrane, subepithelial spikes

Focal segmental glomerulosclerosis• A cause of nephrotic syn drome and chronic kidney d isease.• It generally p resents i n young adults.

Causes

1) idiopathic

2) secondary to other renal pathology e .g. IgA nephropathy, reux n ephropathy

3) HIV

4) heroin

5) Alport's s yndrome

6) sickle-cell

Focal segmental glomerulosclerosis i s n oted for having a high recurrence rate in renal

transplants .

,2


39/81

Sclerosis o f the glomerulus i s se en next to Bowman's ca psule

Sclerosis i s s een in the perihilar region of the glomerulus

IgA nephropathy• also called Berger's disease or mesangioproliferative glomerulonephritis• commonest cause of glomerulonephritis worldwide• thought to be ca used by mesangial deposition of IgA immune co mplexes• there is co nsiderable pathological overlap with Henoch-Schonlein purpura (HSP)

Histology:⇒ mesangial hypercellularity,⇒ positive immunouorescence for IgA & C3

,4


40/81

Proliferation and hypercellularity o f the mesangium is se en in the g lomerulus

Presentations• young male, recurrent episodes o f macroscopic h aematuria• typically associated with mucosal infections e.g., URTI• nephrotic range proteinuria is rare• renal failure

Associated conditions• alcoholic c irrhosis• coeliac disease/dermatitis herpetiformis•

Henoch-Schonlein purpura

Management• steroids/immunosuppressants not be shown to be useful

Prognosis• 25% of patients d evelop ESRF• markers o f good prognosis: frank haematuria• markers o f poor prognosis:

1)male g ender,2)proteinuria (especially > 2 g/day),3)hypertension , hyperlipidaemia4)smoking , ,5)ACE genotype DD

Differentiating between IgA nephropathy and post-streptococcal glomerulonephritis/#


41/81

1) post-streptococcal glomerulonephritis is associated with low complement levels

2) main symptom in post-streptococcal glomerulonephritis i s proteinuria (although haematuria

can occur)

3) there is typically an interval between URTI a nd the onset of renal problems i n post-

streptococcal glomerulonephritis


42/81

Immunostaining for IgA in a patient with HSP

Treatment

analgesia for a rthralgiaTreatment of nephropathy is g enerally supportive .

There is i nconsistent evidence for the use of steroids a nd immunosuppressants ( used if

severe or deteriorating disease)

All patients $it# HTN and proteinuria )> 1 g/day -* s#oul" be starte" on ) ACE) inhibitor ,

+nce t#e (P #as been controlle" s#e s#oul" #a e a renal biopsy , an" if t#is s#o$e" c#anges of

a crescentic glomerulonephritis (GN) t#en an immunosuppression regime similar to t#at use"in renal asculitis s#oul" be starte" (high dose steroids !/" cyclophosphamide)#

Prognosis• usually excellent , HSP is a self-limiting condition, especially in children without renal

involvement• around 1/3rd of patients h ave a relapse

/+


43/81

embranoproli&erative glomerulonephritis• also known as m esangiocapillary g lomerulonephritis• may present as n ephrotic syn drome, haematuria or proteinuria poor prognosis

Type 1• accounts for 90% of cases• subendothelial immune deposits of electron dense material resulting in a 'tram-track'

appearance•

cause: cryoglobulinaemia , hepatitis C

Type 2 - 'dense deposit disease' DDD• causes: partial lipodystrophy , factor H deciency reduced serum complement C3b nephritic factor (an antibody a gainst C3bBb) found in 70%

/,


44/81

Type 3• causes: hepatitis B and C

Management• steroids m ay be effective

$asculitis-ee rheumatology

6ranulomatosis 'ith polyangiitis(BegenerCs granulomatosis )

• Granulomatosis w ith polyangiitis i s n ow the preferred term for Wegener's g ranulomatosis.• an autoimmune condition associated with a necrotizing granulomatous v asculitis , affecting

both the upper and lower respiratory tract a s w ell as the kidneysFeatures:

1) upper r espiratory tract: e pistaxis, sinusitis, nasal crusting

2) lower r espiratory tract: dyspnoea, haemoptysis, cavitating lesions

3) rapidly progressive glomerulonephritis ('pauci-immune', 80% of patients)

4) saddle-shape nose deformity

//


45/81

5) also: vasculitic ras h, eye involvement (e.g. proptosis ), cranial nerve lesions

Investigations:

1) cANCA positive in > 90%, pANCA positive in 25%

2) chest x-ray: wide variety o f presentations, including cavitating lesions

3) renal biopsy: epithelial crescents in Bowman's capsu le

Management:

1) steroids

2) cyclophosphamide ( 90% response)

3) plasma exchange

4) median survival = 8-9 years

Chest x-ray from a young male patient

with granulomatosis with polyangiitis.

Whilst the changes are subtle itdemonstrates a number of ill-dened

nodules t he largest of which projects o ver

the dome of the right hemidiaphragm.

This nodule appears t o have a c entral

lucency sug gesting cavitation

CT of the same p atient showing the

changes in a m uch more obvious way,conrming the presence of at least 2

nodules , the larger of the two having a

large central cavity a nd air-uid level


46/81

• tumours• pregnancy• ciclosporin, the Pill• SLE, HIV

Investigations:• full blood count: anemia, thrombocytopaenia, fragmented blood lm• U&E: acute renal failure• stool culture

Management:• treatment is supportive e .g. Fluids, blood transfusion and dialysis i f required• there is no role for antibiotics , despite the preceding diarrhoeal illness in many p atients The indications for plasma exchange in HUS are complicated. As a general rule plasma

exchange is r eserved for severe cases o f HUS not associated with diarrhea

% S is a complication of infection $it# erocytotoxin pro"ucing Escherichia coli usually oft#e serotype /0:%0.1oxins pro"uce" in t#e intestine enter t#e bloo" an" bin" to en"ot#elial cells in target organs.2n"ot#elial cell "amage lea"s to platelet an" fibrin "eposition $it# resultant fragmentationof circulating re" bloo" cells an" micro ascular occlusion.1#e syn"rome #as also been reporte" after infections $it# coxsackie, ec#o irus an" Shigella .% S is c#aracterise" by t#e su""en onset of #aemolytic anaemia $it# fragmentation of

re" bloo" cells, t#rombocytopenia an" acute renal failure after a pro"romal illness of acutegastroenteritis often $it# bloo"y "iarr#oea.Clinical signs inclu"e increasing pallor, #aematuria, oliguria an" purpura. 3aun"ice isoccasionally seen. %ypertension may be present.1ypical results s#o$ an anaemia, t#rombocytopenia, an" often a neutrop#ilia. (loo" films#o$s fragmente" eryt#rocytes.

There is normal coagulation and $ibrinogen#Neurological complications inclu"e: Stroke, sei4ure an" coma occur in 5/6 of patients7arely pancreatitis, an" Pleural an" pericar"ial effusions.

Approximately /6 of patients $ill "e elop en" stage renal failure.8ong term renal se9uelae range from proteinuria to c#ronic renal failure.1#erapy is supporti e $it#:

• Correction of anaemia• Correction of uraemia by early "ialysis

• Strict flui" balance

/"


47/81

• 1reatment of #ypertension.

%a&or di$$erential diagnosis is'1) Sepsis $it# D!C - presents $it# abnormalities of clotting parameters.

) 11P - t#rombotic t#rombocytopenic purpura presents $it# microangiopat#ic #aemolyticanaemia, t#rombocytopenic purpura, neurologic abnormalities, fe er, an" renal "isease.7enal abnormalities ten" to be more se ere in % S.

Alt#oug# once consi"ere" ariants of a single syn"rome, recent e i"ence suggests t#att#e pat#ogenesis of 11P an" % S is "ifferent.Patients $it# 11P lac a plasma protease t#at is responsible for t#e break"o$n of on

illebran" factor ) ;* multimers an" t#ese accumulate in t#e plasma. 1#e acti ity of t#isprotease is normal in patients $it# % S.

ntil t#e test for ; protease acti ity becomes a ailable, "ifferentiation bet$een % San" 11P is base" on t#e presence of central ner ous system in ol ement in 11P an" t#emore se ere renal in ol ement in % S.

!n % S < 6 of patients are c#il"ren an" a #istory of pro"romal "iarr#oeal illness is morecommon.1#e t#erapy of c#oice for 11P is plasma exc#ange $it# fres# fro4en plasma.

H%$: renal in&ol&ement Renal involvement in HIV patients m ay o ccur as a co nsequence of treatment o r the virus

itself.• Protease inhibitors such as indinavir can precipitate intratubular crystal obstruction• HIV-associated nephropathy (HIVAN) accounts for up to 10% of ESRD ca ses in the US.• Antiretroviral therapy has been shown to alter the course of the disease.

There are ve key features o f HIVAN:

1) normal or large kidneys

2) normotension

3) massive proteinuria

4) elevated urea and creatinine

5) FSGS with focal or global capillary c ollapse on renal biopsy

holesterol embolisation• cholesterol emboli may break off causing renal disease• seen more commonly in arteriopaths , abdominal aortic aneurysms

/


48/81

Features

1) eosinophilia

2) purpura

3) livedo reticularis

4) renal failure

Plasma e(changeIndications for plasma exchange

• Guillain-Barre syndrome• myasthenia g ravis• TTP/HUS• cryoglobulinaemia• Goodpasture's syndrome• ANCA positive vasculitis e.g. Wegener's, Churg-Strauss• hyperviscosity synd rome e.g. secondary to myeloma, monoclonal gammopathy

In most conditions 5 % albumin is t he plasma substitute of choice , except for TTP where we use

FFP as it has a therapeutic role in replacing the missing factor, ADAMTS-13 .

Peritoneal dialysisPeritoneal dialysis ( PD) is a form of renal replacement therapy. It is s ometimes u sed as a stop-

gap to haemodialysis o r for younger patients w ho do not want to have to visit hospital three times

a week.

The majority o f patients d o Continuous A mbulatory P eritoneal Dialysis ( CAPD), which involves

four 2-litre exchanges/day.

Complications:1) Peritonitis:

⇒ Coagulase-negative staphylococci such as Staphylococcus epidermidis is the most

common cause .⇒ Staphylococcus aureus is another common cause

2) sclerosing peritonitis/2


49/81

PD peritonitis• PD peritonitis i s a n emergency and requires p rompt broad spectrum antibiotic t herapy.• Antibiotics delivered through the intra-peritoneal route are preferred to intravenous route.• Whilst antibiotic p olices d iffer among hospitals, initial antibiotic r egimes s hould cover Gram

positive (including MRSA) and Gram negative organisms.• Although laboratory tests are helpful, antibiotic therapy should not be delayed for the

results o f these tests ( CBC, CRP, C/Ss).

Renal &ascular disease• Renal vascular disease i s m ost commonly due to atherosclerosis (> 95% o f patients).• It is associated with risk factors such as smoking and HTN that cause atheroma e lsewhere in

the body.• It may present as HTN, CKD or 'ash' pulmonary oedema .

• In younger patients h owever bromuscular dysplasia (FMD) needs t o be considered.• FMD is more common in young women a nd characteristically h as a 'string of beads'

appearance o n angiography.• Patients respond well to balloon angioplasty ?????

Investigation• MR angiography is no w the investigation of choice• CT angiography

• conventional renal angiography is less com monly pe rformed used nowadays, but maystill have a role when planning surgery

Renal artery s tenosis (RAS)

/4


50/81

• The current evidence favours m edical therapy in these patients, that is, an antiplatelet

agent (aspirin), lipid lowering therapy ( simvastatin) and tight blood pressure control

(amlodipine).• RAS is of ten unmasked when patients com mence a n ACE inhibitor, as t hese d rugs reduce

vasoconstriction in the efferent arterioles, which in turn reduces glomerular ltration

pressure. In patients with critical RAS this can often prompt a precipitous drop in

glomerular ltration rate.

• The recently reported ASTRAL trial was a randomised controlled trial (RCT) comparing

medical and interventional (renal artery angioplasty and stenting) approaches to treating

RAS.• It found that revascularisation carried signicant risks and conferred no signicant clinical

benet.

• There is s ome controversy over the trial recruitment strategy a s i t only included patientswith established RAS where the responsible clinician was "unsure if revascularisation

would be benecial", but for now current practice is t o avoid routine referral for intervention

in newly diagnosed R AS.

• It is m ost important to control his blood pressure, but with an alternative to ACE inhibition

in the rst instance. Cautious, low dose ACE inhibition is s ometimes a n option in these

patients w hen other agents h ave failed to reduce the blood pressure, but this s hould only

occur under close supervision.

Renal artery s tenosis i s a potential cause of hypertension.Typically patients are vasculopaths and poor prognosis (80% mortality at ve years) is

related to concurrent coronary d isease.It is a lmost exclusively c aused by a therosclerosis, but other causes i nclude bromuscular

dysplasia, vasculitis a nd external compression.

Typical ultrasound c hanges a re asymmetrical kidneys; the a ffected kidney > 2 c m smaller

than the unaffected kidney.

0#


51/81

ACE inhibitors are contraindicated in renal artery stenosis as they inhibit the contraction of

the efferent arterioles which promote glomerular ltration in the disease.

Retroperitoneal )brosisLower back pain is the most common presenting feature

Associations

1) Riedel's thyroiditis

2) previous radiotherapy

3) sarcoidosis

4) inammatory a bdominal aortic a neurysm

5) drugs: methysergide

Renal stonesRisk factors

1) dehydration01


52/81

2) hyperparathyroidism, hypercalciuria, hypercalcaemia

3) cystinuria

4) high dietary oxalate

5) renal tubular acidosis

6) medullary sp onge k idney, polycystic kidney disease

7) beryllium or cadmium exposure

Risk factors for urate s tones

1) gout

2) ileostomy : loss of bicarbonate and uid results in acidic urine , causing the precipitation

of uric acid

Drug causes

1) drugs t hat promote calcium stones: st eroids, loop diuretics, acetazolamide, theophylline2) thiazides c an prevent calcium stones ( increase distal tubular calcium resorption)

%magingThe table b elow summarises the a ppearance of different types of renal stone o n x-ray

ype re=uency adio*rap. appearance

1alcium o!alate 70$ pa=ue

;i!ed calcium o!alate/p.osp.atestones

2%$ pa=ue

1alcium p.osp.ate #0$ pa=ue

riple p.osp.ate stones" #0$ 3pa4ue

Urate stones %-#0$ Radio lucent

1ystine stones #$ Semi opa4ue, 5ground glass5 appearance

?ant.ine stones


53/81

• Ureaplasma urealyticum and Proteus infections predispose to their formation (Urease

producing bacteria )

Renal stones management5Acute management of renal colic

Medication•

the British Association of Urological Surgeons (BAUS) recommend diclofenac (intramuscular/oral) a s the analgesia of choice for renal colic*

• BAUS also e ndorse the widespread use of alpha-adrenergic blockers to aid ureteric s tone

passage

*Diclofenac u se i s no w less co mmon following the MHRA warnings ab out cardiovascular r isk .

It is t herefore likely t he guidelines w illchange soon to an alternative NSAID such as naproxen

Imaging• patients p resenting to the Emergency Department usually have a KUB x-ray (shows 60% of

stones)• The imaging of choice is a non-contrast CT (NCCT). 99% of stones a re identiable on

NCCT. Many GPs now have direct access to NCCT

⇒ Stones < 5 mm will usually pass sp ontaneously.⇒

Lithotripsy and nephrolithotomy may be for severe case s .Prevention of renal stones

A) Calcium stones may be due t o hypercalciuria , which is f ound in up to 5-10% of the general

population.

1) high uid intake

2) low animal protein,

3) low salt diet (a low calcium diet has n ot been shown to be s uperior to a n ormocalcaemic

diet)

4) thiazides d iuretics ( increase distal tubular calcium resorption)

B) Oxalate stones:

TTT:• cholestyramine reduces u rinary o xalate secretion• pyridoxine reduces u rinary o xalate secretion

Oxalate stones a re uncommon in dietary e xcess o f oxalate.0,


54/81

However enteric o xaluria may occur in a number of disorders i n which malabsorption results

in excessive colonic absorption of oxalate. These include:1) Coeliac d isease2) Crohn's disease3) Chronic p ancreatitis, and4) Short bowel syndrome.

High uid intake and calcium carbonate a re mainstay of prevention .

C) Uric acid stones allopurinol• urinary alkalinization e .g. oral bicarbonate

Renal stones

Type of

stones Features

Percentage o f

all calculi

Calcium

oxalate

• Hypercalciuria is a major risk factor (various causes)• Hyperoxaluria may a lso increase risk• Hypocitraturia increases r isk because citrate forms

complexes w ith calcium making it more soluble• Hyperuricosuria may cause uric a cid stones t o which calcium

oxalate binds

Stones are radio-opaque (less t han calcium phosphate stones)

85%

Cystine • Inherited recessive disorder of transmembrane cystine transport leading to decreased absorption of cystine from

intestine and renal tubule• Multiple stones may form• Relatively radiodense b ecause they co ntain sulphur

1%

Uric acid • Uric a cid is a product of purine metabolism• May p recipitate when urinary p H low• May be caused by diseases w ith extensive tissue

breakdown e .g. malignancy• More common in children with inborn errors of metabolism

5-10%

0/


55/81

Type of

stones Features

Percentage o f

all calculi

• Radiolucent

Calciumphosphate

• May o ccur in RTA , high urinary p H increases supersaturationof urine with calcium and phosphate

• RTA types 1 and 3 increase risk o f stone formation (types 2

and 4 d o not)• Radio-opaque stones ( composition similar to bone )

10%

Struvite • Stones formed from magnesium, ammonium and phosphate• Occur as a result of urease producing bacteria (and are thus

associated with chronic infections )• Under the alkaline co nditions p roduced, the crystals c an

precipitate• Slightly radio-opaque

2-20%

Effect of urinary pH on stone formation

• Urine pH will show individual variation ( from pH 5-7). • Post prandially the pH falls a s p urine metabolism will produce uric a cid.• Then the u rine becomes m ore a lkaline ( alkaline tide ).• When the stone is n ot available for analysis t he p H of urine may help to determine which stone

was p resent.

Stone type Urine acidity Mean urine pH

Calcium phosphate Normal- alkaline >5.5

Calcium oxalate Variable 6

00


56/81

Stone type Urine acidity Mean urine pH

Uric acid Acid 5.5

Struvate Alkaline >7.2

Cystine Normal 6.5

auses of Sterile pyuria:1) partially t reated UTI2) urethritis e.g. Chlamydia

3) renal tuberculosis

4) renal stones

5) appendicitis

6) bladder/renal cell cancer

7) adult polycystic kidney disease

8) analgesic n ephropathy

Renal cell cancer• Renal cell cancer is a lso known as h ypernephroma• Accounts for 85% of primary renal neoplasms.• It arises from proximal renal tubular epithelium

Associations*

1) more common in middle-aged men

2) smoking

0"


57/81

3) von Hippel-Lindau syndrome

4) tuberous sc lerosis

*incidence of renal cell cancer is o nly s lightly increased in patients w ith ADPCKD

Features:

1) classical tri ad : haematuria, loin pain, abdominal mass

2) pyrexia of unknown origin FUO

3) left varicocele (due to occlusion of left testicular vein)

4) endocrine effects :⇒ may s ecrete erythropoietin ( polycythaemia ),⇒ renin ,⇒ PTH ( hypercalcaemia ),⇒ ACTH

5) 25% have metastases a t presentation

Management:

1) for conned disease a partial or total nephrectomy depending on the tumour size

2) alpha-interferon and interleukin-2 have been used to reduce tumour size and also treat

patients w ith metatases

3) receptor tyrosine kinase inhibitors (e.g. sorafenib , sunitinib ) have been shown to have

superior efficacy c ompared to interferon-alpha

Coronal CT scan o f a m iddle-aged woman with renal cell cancer. Note t he heterogeneously enhancing mass

at the upper pole of the right kidney

0


58/81

Left: normal kidney. Right: 'clear-cell' pattern of renal cell carcinoma

'Clear-cell' pattern of renal cell carcinoma - clear cytoplasm, small nuclei

1#is C1 "emonstrates a #uge left si"e" renal mass t#at is exten"ing into t#e renal ein=!VC an" is most likelya renal cell carcinoma.

02


59/81

BilmsC tumour• Wilms' nephroblastoma is one of the most common childhood malignancies .• It typically presents in children under 5 years of age, with a median age of 3 years o ld

Features:• abdominal mass ( most common p resenting feature) painless haematuria ank pain• other features: anorexia, fever• unilateral in 95% of cases• metastases a re found in 20% o f patients ( most commonly lung )

Associations:

1) hemihypertrophy

2) Beckwith-Wiedemann syndrome : an inherited condition associated with organomegaly,

macroglossia, abdominal wall defects, Wilm's t umour and neonatal hypoglycaemia.

3) as p art of WAGR syn drome with Aniridia, Genitourinary m alformations, mental

Retardation, also WT1 gene deletion.

4) one-third of cases a re associated with a mutation in the WT1 gene on chromosome 11

Aniridia (absence o& the iris ) The is sometimes instead given as Dgonadoblastoma D since the genitourinaryanomalies are tumours o& the gonads ( testes or ovaries ).( A subset of A>7 syn"rome patients s#o$s se ere c#il"#oo" obesity ? t#e

acronym *AG+, )+ for +(2S!1@ * use" to "escribe t#is category )

Management: nephrectomy

chemotherapy radiotherapy if advanced disease• prognosis: good, 80% cure rate

04

https://en.wikipedia.org/wiki/Aniridiahttps://en.wikipedia.org/wiki/Iris_(anatomy)https://en.wikipedia.org/wiki/Testishttps://en.wikipedia.org/wiki/Ovaryhttps://en.wikipedia.org/wiki/Childhood_obesityhttps://en.wikipedia.org/wiki/WAGR_syndrome#60542472https://en.wikipedia.org/wiki/Iris_(anatomy)https://en.wikipedia.org/wiki/Testishttps://en.wikipedia.org/wiki/Ovaryhttps://en.wikipedia.org/wiki/Childhood_obesityhttps://en.wikipedia.org/wiki/WAGR_syndrome#60542472https://en.wikipedia.org/wiki/Aniridia


60/81

Histological features i nclude epithelial tubules, areas o f necros is, immature glomerular structures, stroma with

spindle c ells a nd small cell blastomatous t issues r esembling the metanephric b lastema

Renal transplant

HLA typing and graft failure

• The human leucocyte a ntigen (HLA) sy stem is t he name given to the major histocompatibility

complex (MHC) in humans.• It is c oded for on chromosome 6 .• Some basic points on t he HLA system:

Class 1 a ntigens include A, B and C.Class 2 an tigens include DP,DQ and DR

when HLA matching for a r enal transplant the r elative importance of the HLA antigens a reas f ollows DR > B > A

Graft survival

• 1 year = 90%, 10 years = 60% for cadaveric transplants• 1 year = 95%, 10 years = 70% for living-donor transplants

Post-op problems

• ATN of graft• vascular thrombosis• urine leakage UTI

"#


61/81

Hyperacute ac ute rejection (minutes to hours)

• due to pre-existent antibodies against donor HLA type 1 antigens ( type II hypersensitivity

reaction)• rarely s een due to HLA matching

Acute g raft failure (< 6 months)

• Usually due to mismatched HLA . Cell-mediated (cytotoxic T cells)• may be reversible with steroids and immunosuppressants• other causes i nclude CMV

Causes o f chronic g raft failure (> 6 months)• both antibody and cell mediated mechanisms ca use brosis t o the graft ( CAN )• recurrence of original renal disease ( MCGN > IgA > FSGS )

Fluid therapy:• The prescription of intravenous uids i s o ne of the most common tasks that junior doctors

need to do.• The typical daily requirement is:

1.5 m l/kg/hr uid - for a 8 0kg man around 2-3 liters/day40-70 mmol potassium70-150 mmol sodium

• This is why the typical regime prescribed for patients is:

1 litre 5% dextrose with 20mmol potassium over 8 hours1 litre 0.9% normal saline with 20mmol potassium over 8 hours1 litre 5% dextrose with 20mmol potassium over 8 hours

• The amount of uid patients r equire obviously va ries a ccording to their recent and pastmedical history. For example a patient who is p ost-op and is h aving signicant losses f romdrains w ill require more uid whereas a patient with heart failure should be given less uid to

"1


62/81

avoid precipitating pulmonary o edema.

The table below shows t he electrolyte concentrations (in millimoles/litre ) of plasma and themost commonly used ui ds:

a @ 1l - @ 1 3 - 1a 2@

Plasma 1$'1&' 6017' $-'' ## #0 #-$#-2

0'4$ normalsaline

1'7 1'7

%$ de!trose

artmann,ssolution

1$1 111 ' #6 #

Hyponatraemia:• Hyponatraemia may b e caused by water excess o r sodium depletion.

• Causes of pseudohyponatraemia includeHyperlipidaemia ( increase in s erum volume) or a

taking blood from a drip arm.• Urinary so dium and osmolarity levels a id making a diagnosis

Urinary sodium > 20 m mol/lSodium depletion, renal loss (patient often hypovolaemic )

diureticsAddison'sdiuretic stage of renal failure

"+


63/81

Patient often euvolaemic :

SIADH (urine osmolality > 5 00 mmol/kg)Hypothyroidism

Urinary sodium < 20 m mol/l

Sodium depletion, extra-renal loss

diarrhoea, vomiting, sweatingburns, adenoma of rectum

Water excess:(Patient often hypervolaemic and oedematous)

secondary hyperaldosteronism: heart failure, cirrhosisreduced GFR: renal failureIV dextrose,psychogenic po lydipsia

Hyponatraemia: correctionCentral pontine myelinolysis

• demyelination s yndrome c aused by rapid correction o f chronic hyponatraemia• may lead to quadriparesis and bulbar p alsy• diagnosis: MRI brain

Hypernatraemia: Causes

dehydration• osmotic diuresis e .g. HONK coma DI

",


64/81

• excess IV salineCerebral oedema:• Hypernatraemia should be corrected with great caution. Although brain tissue can lose sodium

and potassium rapidly, lowering of other osmolytes ( and importantly water) occurs a t a slowerrate, predisposing to cerebral oedema

• Resulting in seizures, coma and death .•

It is generally accepted that a rate of no greater than 0.5 mmol/hour c orrection is appropriate.

hypokalaemia:ECG features of hypokalaemia

• U waves• small or absent T waves ( occasionally inversion)• prolong P R interval• ST depression• long QT

The ECG below shows typical U waves. Note a lso t he borderline P R interval

One registered user suggests t he following rhyme• In Hypokalaemia, U have n o Pot and no T, but a long PR and a long QT

ECG changes seen in hyperkalaemia include tall-tented T waves, small P waves, widened QRSleading to a sinusoidal pattern and asystole.

"/


65/81

Hypomagnesaemia:Causes:

• Diuretics, gittelman syndrome• total parenteral nutrition TPN• diarrhoea• alcohol• hypokalaemia, hypocalcaemia

Features: hypocalcaemia BC• paraesthesia• tetany• seizures• arrhythmias• decreased P TH secretion → hypocalcaemia• exacerbates digoxin toxicity• ECG features si milar to those of hypokalaemia

Hypermagnesaemia : EFGHIJK MN*+,- ./ 0123• Nausea, Drowsiness• Double vision• Vasodilatation, and• Hypotension (myocardial depression + vasodilatation).• Bradycardia• Respiratory de pression• Loss of deep tendon reexes• Coma, and• Cardiac a rrest.

Hypophosphataemia:Causes:

• alcohol excess acute liver f ailure DKA refeeding syndrome primary h yperparathyroidism osteomalacia

Consequences:

"0


66/81

• haemolysis• WBC and platelet dysfunction muscle weakness and rhabdomyolysis• CNS dysfunction

The following notes a re so me co mments on important questions from on examination I did nothave time to rearrange it now may b e latter on I will rearrange.9!alate stone

ide 0 mg daily andregular pyrido!ine 1# mg daily can reduce hypero!aluria.

alcium phosphate stones can be prevented 'ith thia4ide diuretics and a lo!calcium diet (restrict dairy products).

5riple phosphate stones o&ten cause staghorn calculi and patients re:uireprophylactic antibiotics to prevent recurrent in&ectionsE these stones may re:uiresurgery &or removal.

""


67/81

6rate stones may be prevented by giving regular allopurinol and by urinaryalkalinisation.

ethods o& preventing cysteine stones include ade7uate hydration (increasedaily ;uid intake) lo! methionine diet D8penicillamine and urinaryalkalinisation .

Acute interstitial nephritis characterised by interstitial in;ammation and oedema.%e&t untreated this results in interstitial 8brosis. A de8nitive diagnosis is establishedby renal biopsy although eosinophiluria and gallium " scanning are also suggestive."# #@ o& cases o& acute interstitial nephritis are induced by e!posure to drugs. Themechanism is via a delayed 58cell hypersensiti&ity or cytoto(ic 58cell reaction .

This is not typically dose dependent. ultiple medications have been implicated andthe presentation and laboratory 8ndings vary according to the class o& drug involved.Agents 'hich are commonly implicated are5

• beta lactam antibiotics (especially methicillin)• sulphonamides• N-AIFs• diuretics (thia>ides &urosemide)• antivirals (aciclovir &oscarnet)• allopurinol and• cyclosporin.

3lassic presenting &eatures include &ever maculopapular rash and arthralgia. ildeosinophilia is common and eosinophiuria is pathognomonic.3essation o& the causative agent is critical in the treatment o& acute interstitialnephritis.3orticosteroids can have a bene8cial e?ect especially i& initiated early.In general the prognosis o& drug induced acute interstitial nephritis is good andpartial or complete recovery o& renal &unction is normally seen.

6oodpastureCs disease is an auto immune pulmonary renal syndrome due tocirculating antibody to the glomerular basement membrane.

In the acute setting treatment is &ocused on managing li&e threatening complicationso& renal &ailure such as hyperkalaemia and removing the circulating auto antibodyresponsible &or disease.

"


68/81

As this patient is receiving haemodialysis the most important treatment in acutesetting is plasmapharesis (therapeutic plasma e!change) as this 'ill remove thecirculating antibody.

There is no role &or intravenous immunoglobulins in the management o& this disease.

In this scenario the recent prescription o& N-AIFs a&ter the patientCs hospitalattendance is the likely cause o& the renal decline. N-AIFs reduce glomerularper&usion by inhibiting production o& prostaglandins 'hich dilate the a?erent arterioleo& the glomerulus. The reduction in blood supply to the kidney results in impairmento& kidney &unction.

As a rule one should be cautious about prolonged prescription o& N-AIFs in theelderly or in those 'ith e!isting renal impairment.

ed kidneys on ultrasound scan and• &ocal segmental glomerulosclerosis on renal biopsy.

*atients also have raised immunoglobulins and raised cholesterol.-ome'hat surprisingly the blood pressure o& patients 'ith


69/81

'here the patient &alls into the hypertensive DemergencyD as here rather than thehypertensive DurgencyD category.

The concern is that i& blood pressure reduction is targeted more aggressivelydisordered autoregulation may result in signi8cant end organ damage.

IG therapy 'ith either sodium nitroprusside or labetolol is the initial therapy o&choice.

Alternatives include phentolamine or hydrala>ine.

Renal vein thrombosis is o&ten clinically silent. Association 'ith hypercoagulablestate peripheral leg oedema and ;ank pain in a patient presenting 'ith AHI are allpertinent clues.

*atients 'ith renal vein thrombosis usually report rapidly 'orsening peripheral legoedema and may report dull loin pain &rom the a?ected kidney.

This patient re:uires screening &or inherited and ac:uired disorders o& coagulationand anti coagulation. -he 'ill re:uire li&elong 'ar&arinisation.

Acute interstitial nephritis is in;ammation o& the renal tubulo interstitium secondaryto a hypersensitivity reaction to drugs. The most common drug related cause isN-AIFs.9ther precipitating drugs includeAntibacterials (penicillins cephalosporins sulphonamides ri&ampicin)%oop diuretics (&urosemide)

Thia>ide diureticsAmphotericin3imetidineAllopurinol.

"4


70/81

7eatures include acute most commonly oliguric renal &ailure 'ith or 'ithoutsystemic &eatures 'hich include &ever arthralgia and skin rashes. any patientshave eosinophilia raised serum Ig and eosinophiluria.Renal biopsy sho's oedema o& the interstitum 'ith in8ltration o& plasma cellslymphocytes and eosinophils 'ith acute tubular necrosis and variable tubulardilatation.

The treatment includes 'ithdra'al o& the o?ending drug and may involve dialysisuntil normal renal &unction returns.

Angiotensin converting en>yme (A3 ) inhibitors can cause acute deterioration inrenal &unction mainly in patients 'ith bilateral renovascular disease and commonly'ithin the 8rst t'o 'eeks o& treatment. A3 inhibitors may also increase the serumpotassium through impairment o& the angiotensin II mediated secretion o&aldosterone. The higher the serum creatinine concentration the greater the risk o&hyperkalaemia.=ncommonly A3 inhibitors may cause progressive renal impairment in patients'ithout renovascular disease especially the elderly 'hich may be caused by amembranous glomerulonephritis.

endro;umethia>ide a thia>ide diuretic inhibits sodium and chloride reabsorption inthe distal convoluted tubule resulting in increased sodium and &ree 'ater clearance.A secondary e?ect is the loss o& potassium by increased secretion in the distal tubulein response to the increased intraluminal sodium. There&ore bendro;umethia>idemay cause hypokalaemia.

Triamterene a potassium sparing diuretic similar to amiloride is occasionally

prescribed 'ith thia>ide or loop diuretics to prevent hypokalaemia. It inhibits themovement o& sodium through channels to'ards the end o& the distal tubule andcollecting ducts preventing the passage o& sodium &rom the urinary space into thetubular cells. This action causes hyperpolarisation o& the apical plasma membranepreventing the secretion o& potassium into the collecting ducts.


71/81

Nephrocalcinosis has not been described in type III mutations there&ore it candi?erentiate bet'een type I and II disease and type III disease.

anagement is 'ith long term potassium supplementation and care to avoiddehydration. The long term prognosis is uncertain.

This patient has had a sudden deterioration in renal &unction three 'eeks &ollo'ing

an uncomplicated renal transplant. Fespite this she is clinically 'ell 'ith nosymptoms.

This lady has acute cellular rejection. Appro!imately +0@ o& transplant patients 'illhave at least one episode o& rejection mostly bet'een days seven and +1 and lesscommonly up to three months post operation. It is o&ten clinically silent 'ith only asharp rise in serum creatinine pointing to'ards the diagnosis.Foppler ultrasound studies may sho' a sharp deterioration in gra&t per&usion andkidney biopsy 'ill sho' invading lymphocytes penetrating the tubular basementmembrane causing tubulitis. Treatment is 'ith IG bolus o& high dose steroids. %ongterm gra&t &unction 'ill be compromised i& the rejection episode is not completelyreversed.3 G in&ection has been associated 'ith increased gra&t rejection and renal arterystenosis in renal transplant recipients.

3iclosporin is a calcineurin inhibitor 'hich is a potent immunosuppressant andnephroto!in. 3iclosporin can cause a dose dependent increase in urea and creatininein the 8rst &e' 'eeks o& taking and also long term gra&t &ailure. This is probablyrelated to the total amount o& ciclosporin taken. in the :uestion they 'ill mentionthat the dose has recently been increased

*yelonephritis o& the transplanted kidney is a particular problem in the early

immunosuppressed period. *yelonephritis 'ould present 'ith lo' grade pyre!iatender s'ollen kidney and deteriorating gra&t &unction.

This lady has longstanding rheumatoid arthritis treated 'ith gold. -he currently hasan e!acerbation o& her symptoms. -he has renal impairment 'ith mild proteinuriaand haematuria.Amyloid is common in patients 'ith longstanding rheumatoid arthritis. The 8brils areamyloid A protein. It presents 'ith proteinuria that is o&ten nephrotic range.6old nephropathy causes proteinuria 'hich is o&ten in the nephrotic range.


72/81

5he clinical presentation in rheumatoid includesNail &old in&arctsA leucocytoclastic vasculitisA peripheral neuropathy*ericarditis6astrointestinal in&arcts andRenal vasculitis.Renal abnormalities are &ound in +0@ o& patients 'ith rheumatoid vasculitis usually

presenting 'ith proteinuria microscopic haematuria and renal impairment.

artterCs syndrome usually presents in childhood 'ith severe muscle 'eakness. It isa salt 'asting state 'hich is due to a de&ect in the loop o& ic acid contained in li:uorice blocking the en>yme 11b hydro!ysteroiddehydrogenase. This prevents the inactivation o& cortisol 'hich in turn activatesmineralocorticoid receptors in the kidney.

This gentleman has a nephrotic syndrome 'ith impairment o& his renal &unction'hich improves markedly 'ith oral prednisolone.

esangiocapillary glomerulonephritis is treated 'ith antiplatelet drugsanticoagulants corticosteroids and alkylating agents. -teroids are given &or aprolonged period o& time and may have some bene8t in some patients.

+


73/81

inimal change glomerulonephritis is e!tremely steroid sensitive 'ith 2#@ o& adultpatients achieving remission 'ithin 1" 'eeks 'ith prednisolone "# mg per day.

This gentleman has had a calcium urinary tract stone. ide diuretics reduce renal tubular calcium e!cretion and there&ore can preventcalcium stone &ormation.%oop diuretics increase urinary e!cretion o& calcium and there&ore 'ould e!acerbatecalcium renal stone &ormation.

=sually the *9 antibody is associated 'ith microscopic polyangiitis 'hereas the*R, antibody is associated 'ith BegenerCs granulomatosis 'hich is closely linked.

Renal biopsy5

7or a routine biopsy there is no pre&erable side to biopsy.

3oagulation studies should al'ays be per&ormed prior to renal biopsy due to the risk

o& bleeding. acroscopic haematuria can occur in up to 1#@ o& renal biopsies.

The hila o& the kidneys lie at the %1 and %+ vertebral levels.

Nephrectomy is a rare but serious complication o& renal biopsy re:uired to controlbleeding. It should be consented &or.

,


74/81

Fairy products are high in phosphate content. 9& the &oods listed cheddar cheese'ill contain the highest phosphate.

*hosphate level is important to control in patients 'ith chronic renal &ailure.

Although high phosphate can cause symptoms such as itching there are long termadverse cardiovascular e?ects.

7oods that are characteristically rich in phosphate include dairy products 8bre rich&oods chocolate and processed meats.

Hidney transplant recipients have a high risk o& developing non melanoma skincancer.

3ancer surveillance is an important consideration in kidney transplant recipients.

ymes capable o& breaking do'n a larger variety o&antibiotics.

In this patient the presence o& renal cysts a reservoir o& in&ection and previousantibiotic use are likely to have led to this resistant strain.

A broad spectrum antibiotic is re:uired and o& the list available meropenem is the

most suitable choice.

Intravenous co amo!iclav is unlikely to be ade:uate. Neither 'ould erythromycinhave the appropriate coverage.

/


75/81

In acute gout 'ith renal impairment a trial o& colchicine is the best option

3olchicine is sa&e to use in renal impairment. It is generally advised to be taken to

the point o& onset o& diarrheal symptoms 'hen its use should be discontinued. -olong as the patient is adherent 'ith the advise renal &unction should not deteriorate

The 8rst line treatment &or acute gout is a non steroidal anti in;ammatory drug(N-AIF) or colchicine. 6iven this patientCs renal impairment a N-AIF 'ould becontraindicated.

*aracetamol 'ill o?er some mild pain relie& but 'ill not treat gout and so is notappropriate.

Allopurinol should not be started in an acute attack o& gout.

*rednisolone is a reasonable choice but is usually tried as a second line treatmenta&ter N-AIF use or colchicine.

In the setting o& diabetes and stable renal &unction the albumin5creatinine ratio is

considered the most appropriate test to detect and :uanti&y proteinuria. Ideally thetest should be per&ormed on an early morning sample.

It is more sensitive than the protein5creatinine ratio &or lo' levels o& proteinuria andmore reliable than a +/ hour urinary collection &or protein.

The albumin5creatinine ratio is the test o& choice in patients 'ith diabetes due to theneed to detect and treat microalbuminuria.

T'enty &our hour urine collections &or protein are &raught 'ith diKculty. Fespite o&tenbeing re&erred to as the Cgold standardC &or measuring proteinuria they are subject toinaccuracies due to incomplete collection o& all urine voided or inaccurate timingand the biochemical methods used to :uanti&y the amount o& protein present givedi?erent results.

7or lo' levels o& proteinuria the *3R is less sensitive than A3R. 9nce signi8cantproteinuria has been detected the *3R may be used &or &ollo' up.

0


76/81

=rine dipsticks are not recommended as a method &or accurately determining'hether there is proteinuria as they cannot reliably detect lo' level protein loss or:uanti&y the amount.

=rine protein electrophoresis may be used i& there is a suspicion o& a urinaryparaprotein (that is ence Lones proteins).

icroalbuminuria is de8ned as an A3R o& +.0 ,# mg$mmol in men and ,.0 ,#mg$mmol in 'omen. This is roughly e:uivalent to the loss o& ,# ,## mg o& albumin inthe urine per +/ hours.

In patients 'ith diabetes microalbuminuria is used as a therapeutic target that canbe modi8ed by renin angiotensin aldosterone system blockade 'ith a resultingimprovement in clinical outcomes.

All patients 'ith diabetes and microalbuminuria should be o?ered therapy 'ith anA3 inhibitor or angiotensin receptor blocker irrespective o& 'hether they havehypertension. The chosen drug should be started at an appropriate starting (lo')dose and titrated up'ards to the target dose as tolerated 'ith monitoring o& renal&unction.

The predominant protein lost in urine is albumin and the albumin5creatinine ratio

nephrology notes 2015

Documents