Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2612_Библиотеки_им_академика_М_И_Перельмана
.pdf
7 Kidney medicine
CKD
CKD
RRT
https://t.me/med1917
bone- mineral disorders
ylation of vitamin
30
(though optimal concentrations are unknown).
<
• Avoid overt hyperphosphataemia (target phosphate in advanced
CKD
D
. Measure calcium, phosphate,
causes in serum phosphate and reduced hydrox-
ALP, PTH,
and
25- OH
vit D if e
CKD
is higher
GFR
than the upper reference limit), whilst avoiding hypercalcaemia. Treatment
is with dietary restriction ± phosphate binders, eg calcium acetate (avoid in
hypercalcaemia), sevelamer, sucroferric oxyhydroxide, lanthanum.
• Give vitamin D supplements (colecalciferol, ergocalciferol) if deficient. If
persists or is increasing, treat with an activated vit
calcitriol.
• Calcimimetics, eg cinacalcet. Used to treat refractory
ation with Ca.
• Bisphosphonates can be given if clinically indicated and e
D
analogue, eg 1- calcidol/
PTH,
and
PTH
GFR
≥30.
PTH
in combin-
Restless legs/ cramps Exclude iron deficiency as a possible exacerbating factor.
Sleep hygiene. Treatment for severe cases with gabapentin/ pregabalin/ dopamine
agonists is o licence: beware of
Diet Expert dietary advice should be available regarding phosphate restriction and
+
if hyperkalaemic, whilst avoiding malnutrition.
K
Management of cardiovascular risk in
CKD
confers risk of
stress, and abnormal endothelial function.
kidney failure
• Consider antiplatelets (low- dose aspirin) if risk for atherosclerotic events, unless
bleeding risk outweighs benefit (mortality benefit unclear in
• Atorvastatin 20mg (higher dose if
CVD
(no consistent benefit demonstrated for patients on dialysis).
of
•
SGLT2
inhibitors if e
•
CKD
should not aect treatment for heart failure but monitoring of
•
GFR
<60 may aect troponin and
CVD
.
GFR >25
Preparation for renal replacement therapy (
Planning for
that
RRT
RRT
should begin in progressive
will be required within 12 months. Shared- decision making, psychological
SE
(falls, cognitive impairment).
due to BP, vascular stiness, inflammation, oxidative
CV
risk is often higher than the risk of
GFR
>30) for primary and secondary prevention
+ indicated for
BNP
concentrations. Interpret results cautiously.
CVD
or heart failure.
)
CKD
when clinical judgement predicts
CKD).
GFR
and K+ .
preparation, work- up for transplantation, modality choice, and access take time.
All suitable patients should be informed about the advantages of a pre- emptive
living kidney transplant and eorts made to find a donor (
tients without a donor should be listed for deceased donor transplantation
6
months before the anticipated start of
RRT
.
p
304
). All suitable pa-
301
Prescribing in
CKD
Never prescribe in kidney disease without checking how administration should
GFR
be altered due to
. This will be determined largely by the extent to which a
drug is excreted by the kidney. This is significant for aminoglycosides, penicillins,
cephalosporins, heparin, lithium, opiates, and digoxin.
Loading doses should not be changed.
If precision is required for dosing (eg chemotherapy) then
mated from creatinine and a standard reference measure should be used: inulin,
51
Cr-
EDTA
,
125
I- iothalamate, iohexol.
If the patient is receiving renal replacement (haemofiltration, peritoneal, or
haemodialysis), dose modification depends on the extent to which a drug is
cleared from the circulation by dialysis/ filtration.
The best prescribing guide to consult is the Renal Drug Database/ Handbook
www.renald rugd atab ase.com), an invaluable resource detailing dose modification in
(
kidney failure and in renal replacement for almost any drug you could wish to use.
All hospitals should have access: speak to your pharmacist.
GFR
should not be esti-
7 Kidney medicine
Renal replacement therapy (
RRT
RRT
removed
in
Blood
turned
Waste out
Post
dilution
Pr
dilution
https://t.me/med1917
302
Long- term dialysis is started when the complications of dialysis are less than
symptoms and complications of advanced
• Inability to control volume status, including BP and pulmonary oedema.
• Acid– base or electrolyte abnormalities resistant to medical treatment.
• Serositis, eg pericarditis.
• Pruritus with anticipated benefit from dialysis.
• Nausea/ vomiting or a deterioration in nutritional status.
• Cognitive impairment due to advanced
RRT
is a misnomer for dialysis: kidney function is not replaced, rather there is
provision of just enough clearance to ameliorate the symptoms of kidney failure.
GFR
at commencement of dialysis is usually ~5– 10. When transplantation is awaited
or not possible, there are two main options: haemodialysis and peritoneal dialysis.
Haemodialysis (HD) (fig
passed over a semi- permeable membrane against dialysis fluid flowing in the
opposite direction. Diusion of solutes
occurs down the concentration gradient.
A hydrostatic gradient is used to clear
excess fluid as required (ultrafiltration).
Access is preferentially via an arteriovenous fistula which provides blood
flow and access longevity. It should be created in advance of
the infection risk associated with central venous catheters.
times/ week. More frequent
HD
should be oered to all suitable patients. Problems Quality of life, access (arteriovenous fistula: thrombosis, stenosis, steal syndrome; tunnelled venous line: infection, blockage, recirculation of blood), dialysis disequilibrium (between cerebral
and blood solutes leading to cerebral oedema start
Peritoneal dialysis (PD) Uses the peritoneum as a semi- permeable membrane.
A catheter is inserted into the peritoneal cavity and fluid (dialysate) infused. Solutes
diuse between blood and dialysate. Ultrafiltration occurs due to osmotic agents
(glucose, glucose polymers) in the dialysate. It is a continuous process with intermittent drainage and refilling of the peritoneal cavity, performed at home.
Catheter site infection,
Haemofiltration (fig
vection. The ultrafiltrate (waste) is replaced with an appropriate volume of (‘clean’) fluid
either before (pre- dilution) or after (postdilution) the membrane. Haemodynamic
instability so used in critical care
used in chronic
HD
(= haemodiafiltration,
RRT
haemodynamic stability and middle
molecule clearance, eg
Requires sucient water quality.
Complications of
• Cardiovascular disease BP, vascular stiness, inflammation, oxidative stress,
endothelial dysfunction, mortality is ×
• Protein- calorie malnutrition Increases morbidity and mortality.
• Renal osteodystrophy Bone turnover, osteitis fibrosa, vascular calcification.
• Infection Access infection, granulocyte and T- cell dysfunction may mortality.
• Amyloid 2- microglobulin deposition: carpal tunnel syndrome, arthralgia.
Conservative management This is for those who opt not to receive
to lack of benefit on quality or quantity of life. Dialysis does not prolong life for
everyone, especially if frail with significant comorbidity. Focus is on preserving residual kidney function, symptom control, and advanced planning for end of life care.
): dialysis and filtration
CKD
. Indications for
CKD
.
7. 6
) Blood is
HD
increases the ‘dose’ and improves outcomes. Home
Fig 7.
Blood
in
Waste
6
Haemodialysis.
RRT
may include:
Blood
Dialysate
RRT
start to avoid
HD
is usually needed 3
HD
gradually), hypotension.
re
Fluid
Problems
PD
peritonitis, hernia, membrane function over time.
7. 7
) Water is cleared by positive pressure, dragging solutes by con-
Blood
Blood
.
Only
in combination with
HDF
). May oer
- microglobulin.
2
20
e-
Fig 7.
7
Haemofiltration.
compared to general population.
in
Blood
Dialysate
returned
RRT
due
7 Kidney medicine
When a patient on dialysis presents...
BP
IV
https://t.me/med1917
1 Do they need dialysis now? Examine for fluid overload and check K
they well enough to perform it themselves? Refer urgently to nephrology.
2
When will they need dialysis? When are they due to dialyse next? Weigh them.
All patients on dialysis have a
euvolaemic. How much are they above it? Do they have any useful urine output
that may help excrete volume/ K
3
What is your diagnosis? History and examination as for any other patient. Do not
measure
have specificity for cardiac injury in advanced
4
Treat. Remember to dose adjust for kidney function. This includes antibiotics,
opiates, insulin, and low- molecular- weight heparin (see
p
on fistula arm. Remember risk for
301
). Care with fluid replacement in sepsis: be guided by clinical examination
and target weight. If unsure get expert help. If volume depleted give a
bolus of crystalloid over
in those who normally have a fluid restriction.
access. If a cannula is necessary, preferentially use the back of the hand,
for
save other vessels for future access.
5
Surgery needs senior anaesthetic and nephrology input. Aim for pre- op K
<5.5
mmol/ L (<5.0mmol/ L if major surgery with risk of tissue breakdown/ haem-
Check K+ urgently via point- of- care testing (venous blood gas) in recov-
olysis).
ery. In elective surgery, plan for dialysis provision pre- and post- operation.
Warning: there is no normal
'Ten years is a long time. For those ten years, or just over 3,
myself to a peritoneal dialysis machine and underwent nine hours and fifty minutes of nightly therapy. I subsequently learned to do a lot of crosswords and read
a ridiculous amount of books. In ten years I had just three incidents: an inguinal
hernia due to thinking that I could move a sofa (I could not), a parathyroidectomy
(my knees were much happier afterwards), and one unfortunate bout of peritonitis (once was enough). Statistically speaking, I am an anomaly: the ‘average’ life
span of a peritoneal dialysis patient is four years.
Admittedly, I did not initially cope well with needing to be on dialysis. After having
lived successfully with a transplant, a return to dialysis felt like failure. I did not
want the hassle of treatment. I did not want piles of boxes cluttering up our home.
Mostly, I did not want a
believed to be unacceptable, gradually became tolerable. This took time. It took
care and support. It took experiencing relative health, and seeing that dialysis life,
although dierent to existing with a transplant, could be lived well.'
Natasha Boone, author and illustrator
The man in a red canoe who saved a million lives
Mostly we commute to work each day driven by motives we would rather not look
at too deeply. But one kidney physician used a red canoe to commute each day
from his houseboat to the hospital. He could have been a very rich man but instead
Belding Scribner gave his invention away, and continued his modest existence.
He invented the Scribner shunt— a
allowing haemodialysis to be repeated as often as needed. Before Scribner, glass
tubes were inserted painfully into vessels, which would be damaged, limiting
haemodialysis to only a few cycles. Clyde Shields was his first patient in
said that his first treatment ‘took so much of the waste I’d stored up out of me
that it was just like turning on the light from darkness’. Scribner transformed a
fatal condition to one with
On
19
June
2003
, his canoe was found empty. And like those ancient Indian burial
canoes found at Wiskam which have been polished to an unimaginable lustre by
the action of the shifting sands around the Island of the Dead, so we polish and
cherish the image of this man who gave everything and took nothing.
+
. If on PD are
target weight at which they are considered
+
? Refer to nephrology in a timely manner.
CVD
but troponin concentrations
CKD
and dialysis.
www.renald rugd atab ase.com,
250
15
min with close observation. Avoid maintenance fluids
Do not use a dialysis line or fistula
650
times, I attached
PD
catheter jutting out of my belly. But what I originally
U
of Teflon™ connecting an artery to a vein,
1960
90
% survival.
mL
, and
+
303
7 Kidney medicine
Renal replacement therapy (
RRT
https://t.me/med1917
304
Transplantation (figs
gressing towards, stage
kidney failure provided risks do not exceed benefits.
Contraindications
• Absolute: cancer with metastases.
• Temporary: active infection,
• Relative: heart failure,
Typ e s of gr af t
• Living donor Better graft function and survival, especially if
• Deceased donor (p13)
1
Donor after brain death (
2
Expa nded cr iteria d onor (
long- term outcome but better anticipated survival/ quality of life than dialysis.
3
Donor after cardiac death (
graft function.
Immunosuppression
A combination of drugs are used. Aim is to use the minimal eective dose with the
lowest drug- related toxicity. Protocol depends upon the immunological risk of the
recipient and type of donated kidney.
Monoclonal antibodies eg bas ilixim ab, dac lizuma b (selectively block activated T cells
CD
- 25), alemtuzumab (T- and B- cell depletion). Used at the time of transplantation
via
(‘induction’). Acute rejection and graft loss.
Calcineurin inhibitors eg tacrolimus, ciclosporin. Inhibit T- cell activation and pro-
liferation. Inter- individual variation and narrow therapeutic window so monitoring
of drug concentrations is required. Clearance via cytochrome
beware of drug interactions including macrolide antibiotics and antifungal drugs.
SE
: nephrotoxicity, BP, cholesterol, new- onset diabetes after transplantation
Anti- metabolites eg mycophenolic acid (
MPA
proliferation.
vival (not in pregnancy,
Mammalian target of rapamycin (m
metabolite/
Glucocorticoids Transcription of inflammatory cytokines. Significant SE (BP,
hyperlipidaemia,
is now used preferentially to acute rejection and graft sur-
CNI
. Theoretical cancer risk but data conflicting
DM
gility) have led to protocols with early withdrawal of steroids and the use of
steroid- free immunosuppression regimens.
Complications
Bleeding, thrombosis, infection, urinary leak, lymphocele, hernia.
Surgical
Delayed graft function Up to 40% of grafts, more common in
be acute or chronic. Acute rejection can be antibody- (rare unless known presensitized recipient, check for donor specific antibodies) or
common). Treat with (short- term) immunosuppression. Chronic rejection is better
termed 'chronic allograft nephropathy' and is a major cause of transplant loss.
Slow immune- mediated damage to the microcirculation leads to inflammation,
remodelling, and irreversible tissue injury.
disease, and infection may also contribute. Umbrella terminology and a lack of controlled studies mean optimum treatments are not known.
Infection Risk of all infections. Typically hospital acquired/ donor derived in month
1
, opportunistic in months 1– 6 (prophylactic treatment for
jirovecii given), usual spectrum of infection after
should be considered: eg
Malignancy Up to 25× risk of cancer with immunosuppression, particularly skin,
post- transplant lymphoproliferative disorder (
CVD
3– 5× risk of premature
BP, NODAT,
lysis).
rejection, and kidney history (uraemic cardiomyopathy) contribute.
): transplantation
7. 8, 7.9
) should be considered for every patient with, or pro-
G5
kidney disease (p
HIV
with viral replication, unstable
CVD,
other comorbidities/ frailty.
DBD
, heart- beating donor).
ECD
) from an older donor or one with
DCD
MPA
is teratogenic). SE: anaemia, leucopenia, GI toxicity.
298
). It is the treatment of choice for
CVD
.
HLA
matched.
CVA, BP
, or
CKD.
Impacts
, non- heart- beating donor) with risk of delayed
SE
: infection risk if non- selective.
P
450
isoenzymes so
MPA
), azathioprine. Inhibit
TOR
) inhibitor eg sirolimus. May replace anti-
. SE
: wound healing.
T-
and
(NODAT)
B-
cell
, impaired wound healing, osteoporosis, cataracts, skin fra-
DCD
.
T
- cell- mediated (most
CNI
- mediated nephrotoxicity, recurrent
CMV
CMV, HSV
.
CVD
compared to population (but ~80% less than dia-
6– 12
PTLD
), and gynaecological.
and Pneumocystis
months. Late viral infection
.
7 Kidney medicine
Prognosis
https://t.me/med1917
Acute rejection <15%, 1- year graft survival >90%. Longer- term graft loss ~4%/ year.
Fac to rs c o nt ri bu ti ng t o gr af t lo ss :
• Donor factors: age, comorbidity, living/ deceased,
• Rejection.
• Infection.
• BP/
CVD.
• Recurrent kidney disease in graft.
DBD/ DCD.
Most common outcome is death with a functioning transplant (ie transplant ‘outlives’ the patient).
When a patient with a kidney transplant presents...
1 Inform the local kidney transplant unit: they will be happy to advise, review,
transfer, and follow- up all kidney transplant recipients.
2
What is the e
you do not have any previous results, ask the transplant unit.
3
Examine for and treat any reversible cause of
is important
and treatment of sepsis should be prompt.
4
Consider viral/ opportunistic infections and atypical presentations due to im-
munosuppression, eg
5
Do not stop immunosuppressive medication. Change in immunosuppression is
led by the transplant unit. If the patient is unable to tolerate oral medication
then immunosuppression should be given
sion depends on drug: check with your pharmacist).
6
Check for medication interactions: eg macrolide antibiotics (erythromycin,
clarithromycin) can cause calcineurin inhibitor toxicity.
7
Dose all drugs according to kidney function: penicillins, cephalosporins, amino-
glycosides, insulin, opiates, and low- molecular- weight heparin.
8
Check with the transplant unit before you give low- molecular- weight heparin
for
GFR
/ creatinine? How does this compare with previous results? If
AKI
—
if you are unsure, get expert help. Correction of volume depletion
CMV
, Pneumocystis jirovecii.
VTE
prophylaxis: they may need to do a transplant biopsy.
. Fluid state assessment (p
NG
or converted to an IV dose (conver-
296
Thank you for life
Dear Donor Family,
I always knew I wanted to write to you. Before I received my transplant, I had been
unwell for many years, and was undergoing dialysis every day. I knew a transplant
wouldn't cure me, but I hoped it would give me back so many things I'd lost through
being sick. I want you to know that I do the best I can every day to look after myself
and my new kidney. I know how lucky I am to have it and taking care of it helps me
to honour the huge gift your loved one has given me. I've thought of him, and of you,
every single day since I had my transplant. I never imagined that people I know so
little about would become such an important part of my life, but you have. I want
you to know that although I am cautious over my health, I am determined to not be
so fearful I miss out on living. Anything less would
be a waste. Because of you, I'm healthier than
I ever thought I would be. For the first time in a
really long time, I'm excited about what's in my
future. Thank you for helping me find that hope.
With love and gratitude, Holly.
Reproduced with kind permission from Holly Loughton.
305
)
Fig 7.
8
‘Alive’ by Natasha Boone.
www.natashaboone.com
Fig 7.
9
Post- transplant scribble by Natasha Boone.
www.natashaboone.com
7 Kidney medicine
Glomerulonephritis
https://t.me/med1917
306
The term glomerulonephritis (GN) encompasses a number of conditions which:
• are caused by pathology in the glomerulus.
• present with proteinuria, haematuria, or both.
• are diagnosed on a kidney biopsy.
• cause
CKD.
• can progress to kidney failure (except minimal change disease).
The names of the diseases come from either histological appearance (eg membranous
glomerulonephritis), or the associated systemic condition (eg lupus nephritis).
Nephrotic or nephritic? The glomerulonephritides classically present on a spectrum
rangi ng from nephrosi s (protein uria due to podocyte pat hology,
(haematuria due to inflammatory damage,
proteinuria can occur in any
the longer- term clinical picture of any
Investigation Assess damage and potential cause.
Blood
FBC, U&E, LFT, CRP
ANA, ANCA
, anti- ds
DNA
Urine u
ACR/ uPCR
Imaging Ultrasound (size and anatomy for biopsy),
Kidney biopsy Required for diagnosis in most (adult) cases.
, anti-
(p
290
Kidney biopsy
Follow local protocol for kidney biopsy.
Pre- procedure BP (<
Written informed consent including complications: mild back/ loin pain, visible
haematuria (~
graphic intervention (~
PT
<1.2, low- molecular- weight heparin 24h).
5
%, usually clears), bleeding, need for transfusion (~1%), angio-
Post- procedure Bed rest for a minimum of 4h. Monitor HR, BP, symptoms, and
urine. Do not discharge home until macroscopic haematuria has settled. Aspirin
or warfarin can be restarted the next day if procedure uncomplicated.
Result Proportion of glomeruli involved (focal vs diuse), how much of each
glomerulus is involved (segmental vs global), hypercellularity, sclerosis. Also
examines tubulointerstitium (atrophy, fibrosis, inflammation) and any vessels.
Immunohistology for deposits (
copy for ultrastructure: precise location of deposits, podocyte appearance.
Management General management as for
renin– angiotensin &
depends on histological diagnosis, disease severity, disease progression, and comorbidity.
SGLT2
p
308
p
307
GN
that causes scarring. Proteinuria can therefore complicate
, immunoglobulins, serum light chains,
GBM
, anti-
),
160/ 95
PLA2R
RBC
casts (p
),
FBC
(Hb >9, plt >
≤
0.5
%). Stop anticoagulants (aspirin 1 week, warfarin to
I
g, light chains, complement). Electron micros-
). This is illustrated in fig
GN
, including those that are classically ‘nephritic’.
Fig 7.
disease from proteinuria (nephrosis) to haematuria (nephritis).
et al., Oxford Textbook of Clinical
Nephrology,
. Blood culture,
291
),
MC&S
CKD
C3, C4
ASOT
.
100
(pp
, hepatitis and
CXR (
pulmonary haemorrhage).
), clotting (PT and
298– 301
) including BP control, and
), to nephritis
7. 1 0
10
Spectrum of glomerular
Figure adapted from Turner
2015
, with permission
from Oxford University Press.
. Aut oant ibo die s (p
HIV
APTT
<1.2),
inhibition. Specific treatment including immunosuppression
. However,
550
serology.
G&S
):
.
7 Kidney medicine
Nephritic glomerulonephritis (GN)
https://t.me/med1917
Nephritic glomerulonephritides8 include:
IgA
ne phropat hy
Commonest primary GN in high- income countries. Historically: Berger’s disease.
Presentation: asymptomatic non- visible haematuria, or episodic visible haema-
12– 72
turia which may be ‘synpharyngitic’: within
1
g. Indolent: 20– 50% progress to kidney failure over 30yrs. Worse prog-
usually <
nosis in ,
Treatment
pression. Immune suppression may be considered if persistent significant proteinuria despite
Henoch– Schönlein purpura (
BP,
creatinine, proteinuria. Diagnosis: IgA deposition in mesangium.
ACE
- i/
ARB
and
SGLT
2
inhibitor (p
ACE
- i/
ARB
, or progressive
HSP
)
h of infection.
300
). Limited evidence for immunosup-
CKD,
but beware SE.
BP.
Proteinuria
Small vessel vasculitis and systemic variant of IgA nephropathy with IgA deposition in skin/ joints/ gut in addition to kidney.
extensor surfaces (typically legs, flitting polyarthritis, abdominal pain, and neph-
Diagnosis: clinical. Confirmed with positive IF for IgA and C3 in skin. Kidney
ritis.
biopsy is identical to
IgA
nephropathy. Treatment: supportive. Steroids may be
used for gut involvement. Kidney disease managed as
Post- streptococcal
GN
Presentation: purpuric rash on
IgA
nephropathy.
Occurs after a throat (~2 weeks) or skin (~3– 6 weeks) infection. Streptococcal antigen deposits in the glomerulus lead to immune complex formation and inflam-
Presentation: varies from haematuria to acute nephritis, ie haematuria,
mation.
BP,
oedema,
anti-
and oliguria. Diagnosis: evidence of streptococcal infection:
DNA
se B. C3. Subepithelial humps on electron microscopy. Tre at me nt : sup-
ASOT
portive, antibiotics to prevent spread of nephritogenic bacteria.
Anti- glomerular basement membrane (anti-
GBM
) disease
Rare. Antibodies to type IV collagen in glomerular and alveolar basement membranes. Historically: Goodpasture’s disease.
guria/ anuria, haematuria,
SOB
, haemoptysis). Oligoanuria, dialysis dependence, crescents on biopsy pre-
dict poor prognosis.
AKI
) and lung disease (alveolar haemorrhage in 40– 60%
Diagnosis: anti-
Presentation: kidney disease (oli-
GBM
in circulation/ kidney (fig
7.11
). Treatment:
plasma exchange (remove circulating antibody), corticosteroids, and cyclophosphamide (stop antibody production).
Rapidly progressive
Aggressive
clude small vessel/
GN
may ‘transform’ to become rapidly progressive including IgA, membranous.
Other
Diagnosis: breaks in the
are seen on kidney biopsy (crescentic
cyclophosphamide. Rituximab increasingly used. Other treatments depend on aetiology, eg plasma exchange for anti-
GN
GN,
rapidly progressing to kidney failure over days/ weeks. Causes in-
ANCA
vasculitis (p
GBM
310
), lupus nephritis (p
310
), anti-
GBM
disease.
allow an influx of inflammatory cells so that crescents
GN
) (fig
7. 1 2
). Tr ea tm en t: corticosteroids and
GBM
, mycophenolate for lupus nephritis (p
310
).
307
,
Fig 7.
11
Immunofluorescence for IgG, showing
linear staining characteristic of anti-
Reproduced from Barratt et al., Oxford Desk
Reference: Nephrology,
2008
from Oxford University Press.
GBM
di s ea se .
, with permission
Fig 7.
12
Crescentic GN: a proliferation of epithelial cells and macrophages with rupture of
Bowman’s capsule.
Reproduced from Turner et al., Oxford Textbook
of Nephrology,
2016
, with permission from Oxford
University Press.
7 Kidney medicine
Nephrotic syndrome
https://t.me/med1917
308
If there is oedema, dipstick the urine to avoid missing kidney disease.
Definition The nephrotic syndrome is a triad of:
• Proteinuria >3g/ 24h (u
• Hypoalbuminaemia (usually <30g/ L, can be <10g/ L).
• Oedema.
Aetiology
• Primary kidney disease Minimal change disease, membranous nephropathy
(may be associated with underlying inflammation/ malignancy), focal segmental
glomerulosclerosis (
• Secondary kidney disease DM, lupus nephritis, myeloma, amyloid, pre- eclampsia.
Pathophysiology The filtration barrier of the kidney is formed of podocytes, the
glomerular basement membrane
• Podocyte pathology: abnormal function in minimal change disease, immune-
mediated damage in membranous nephropathy, podocyte injury/ death in
•
GBM
/ endothelial cell pathology: membranoproliferative GN, inherited abnormalities
in membrane proteins causing disease (Alport’s,
Presentation Generalized, pitting oedema, which can be rapid and severe. Check
dependent areas (ankles if mobile, sacral pad/ elbows if bed- bound) and areas of low
tissue resistance, eg periorbitally.
skin. Consider malignancy and chronic infection.
liver disease (albumin).
Management
1 Reduce oedema
Fluid and salt restriction. Diuresis with loop diuretics, eg furosemide. Give IV if
oral absorption aected. Use daily weights to guide. Aim for
per day depending on severity/ size to try and avoid intravascular volume depletion
and secondary
proteinuria— data that it benefits outcomes are limited and of low quality.
2
Treat underlying cause
Adults need a kidney biopsy (p
DM
+ microvascular complications, positive
AKI
. Thiazide diuretics can be added if resistant. Albumin infusion
first if orthopnoea or subcutaneous oedema at biopsy site. Histology may direct
disease- specific treatment, eg immunosuppression in minimal change disease/
lupus nephritis. In children, minimal change disease is the commonest aetiology
and steroids induce remission in the majority. Biopsy is avoided in children unless
steroid resistant, or if atypical features: age <
ease, kidney failure, haematuria.
3
Reduce proteinuria
ACE
- i/
ARB
reduce proteinuria (may not be needed in minimal change if treatment
response is rapid).
press but criteria are likely to expand, so seek contemporary guidance.
4
Complications
• Thromboembolism: hypercoagulable due to clotting factors, anti- thrombin
renal vein thrombosis (loin pain, haematuria,
risk, consider prophylaxis when albumin <
• Infection: urine losses of immunoglobulins and immune mediators lead to risk of
urinary, respiratory, and
lation: cellulitis, peritonitis, empyema. Ensure pneumococcal vaccination given. Risk
of varicella with steroid treatment: post- exposure prophylaxis in non- immune, do not
give live vaccine if immunosuppressed.
• Hyperlipidaemia: cholesterol (often >
to hepatic synthesis in response to oncotic pressure and defective lipid breakdown.
Proportional to proteinuria. The benefits of statins in
rotic syndrome where there is evidence.
PCR
>
300
mg/ mmol, u
FSGS
), membranoproliferative GN.
(GBM),
ACR
>
250
mg/ mmol, p
and endothelial cells. Proteinuria is due to:
p
316
) or treatment resistance
History Ask about systemic symptoms, eg joint,
CCF
(
JVP
, pulmonary oedema),
306
) if cause unclear. It may not be indicated if
PLA2- R
(p
309
). Diuresis may be required
1
yr, family history, extrarenal dis-
SGLT
2
in proteinuric
CNS
infection. Infection also seen in areas of fluid accumu-
CKD: eGFR
VTE
including
10
mmol/ L),
25
g/ L.
>25 + u
ACR
>25 at the time of
DVT/ PE
(~10% adult patients) and
LDH, AKI
if bilateral). If low bleeding
LDL
, triglycerides,
CKD
are extrapolated to neph-
290
).
0.5– 2
kg weight loss
HDL
FSGS.
.
III
. Attributed
,
7 Kidney medicine
Nephrotic glomerulonephritis
https://t.me/med1917
Nephrotic glomerulonephritides8 include:
Minimal change disease
~25% of adult nephrotic syndrome. Idiopathic (most). Rarely in association with
NSAID
drugs (
S, lithium) or paraneoplastic (haematological malignancy, usually
Hodgkin’s lymphoma). Does not cause kidney failure (if
Diagnosis: light microscopy is normal (hence the name). Electron microscopy
shows eacement of podocyte foot processes (non- specific finding in proteinuria).
Treatment: prednisolone 1mg/ kg 75% of adults will respond within 16 weeks,
50
% relapse. Relapses may need longer- term immunosuppression. Tacrolimus is
>
an alternative for both de novo and relapsed disease.
Foc al s egm enta l gl ome rul osc lero sis (
Commonest glomerulonephritis on kidney biopsy. Primary (idiopathic) or secondary
HIV
, heroin, lithium, lymphoma, any cause of kidney mass/ nephrons, scarring due to
(
another glomerulonephritis). Risk of progressive
worsens prognosis. Primary disease recurs in
Diagnosis: glomeruli have scarring of certain segments (ie focal sclerosis). May
miss early disease if <
Treatment:
Corticosteroids in primary disease: remission in ~
50
%. Calcineurin inhibitors used second line or if SE of steroids are significant.
10
ACE-
i/
ARB
and blood pressure control in all.
Plasma exchange and rituximab have been used for recurrence in transplants.
Membranous nephropathy
~25% of adult nephrotic syndrome. Primary (anti- phospholipase A2 receptor
PLA2- R
) antibody in 70– 80%, thrombospondin type 1 domain- containing 7A anti-
(
3– 5
bodies in
• Malignancy: lung, breast, GI, prostate, haematological.
• Infection: hepatitis
• Immunological disease:
• Drugs: gold, penicillamine.
%), or secondary to:
B/ C
Indolent disease with spontaneous complete remission in ~
Diagnosis:
ened
PLA2- R
GBM
antibody concentrations are prognostic. Biopsy: diusely thick-
, subepithelial deposits (IgG4 dominant in idiopathic, other IgGs in sec-
ondary disease), ‘spikes’ on silver stain where
Treatment:
hibitor (
taneous remission. Immunosuppression for high- risk primary disease, eg nephrosis/
progressive
steroids/ cytotoxics for
inhibitors.
ACE-
i/
ARB
p
306
, blood pressure control, and lipid management.
). Consider
CKD
despite
PLA2- R
antibody concentrations may correlate with disease activity.
Treat underlying cause if secondary disease.
Membranoproliferative glomerulonephritis
~10% of adult nephrotic syndrome (higher in low- and middle- income countries
due to infection). Divided into:
• Immune- complex associated: increased or abnormal immune complexes deposit in
the kidney and activate complement. An underlying cause can be found in most adult
cases, eg infection, cryoglobulinaemia, monoclonal gammopathy, autoimmunity
• C3 glomerulopathy: due to a genetic or acquired defect in the alternative comple-
ment pathway, eg
C3
nep hriti c facto r. P rogres sive ki dney d iseas e is co mmon.
Diagnosis: proliferative glomerulonephritis with electron- dense deposits.
Immunoglobulin deposition distinguishes immune- complex- associated disease
C3
glomerulopathy.
from
Tre at me nt:
ACE-
i/
ARB
and blood pressure control in all.
Expert evaluation of complement pathways may oer utility in tailoring treatment according to aetiology. Underlying cause in immune- complex disease.
C3
Ta rg et ed
therapie s awai ted.
CKD
FSGS
consider missed
)
CKD
and kidney failure: proteinuria
30– 50
% of transplants.
FSGS
glomeruli in biopsy sample.
SGLT2
25
%, partial remission in up to
inhibitor (p
, Streptococcus, malaria, schistosomiasis.
SLE
, rheumatoid arthritis, sarcoidosis, Sjögren’s.
20
%, partial in 20%.
GBM
grows between deposits.
VTE
prophylaxis if albumin <25g/ L. Observation for spon-
ACE-
i/
ARB
inhibition. Options include: rituximab, alternating
6
months ('Ponticelli regimen'), steroids plus calcineurin
SGLT
2
inhibitor (p
SGLT
306
2
in-
306
).
).
).
309
7 Kidney medicine
Systemic disease in the kidney
ANCA
https://t.me/med1917
310
Diabetic nephropathy
DM
nephropathy9 is the commonest cause of end- stage kidney failure: ~30– 40%
of patients requiring renal replacement. Predicted prevalence by
20
years. Hyperglycaemia leads to growth factors, renin– angiotensin–
next
aldosterone activation, production of advanced glycosylation end- products, and
oxidative stress. Causes glomerular capillary pressure, podocyte damage, and
endothelial dysfunction. Microalbuminuria is first clinical sign. Later scarring
(glomerulosclerosis), nodule formation (Kimmelstiel– Wilson lesions), and fibrosis
with progressive loss of kidney function. Coexisting
celerate disease.
increased’) (
Diagnosis Microalbuminuria = u
p
290
, p
tected on standard dipstick must send u
Tre at me nt
• Intensive DM control prevents microalbuminuria and reduces risk of progression to
macroalbuminuria = u
7
%) reduces development of microvascular complications (less impact on
mol (
and kidney outcomes). Consider risk of hypoglycaemia.
• BP <
130/ 80
trol. Can prevent progression from normoalbuminuria to microalbuminuria to
macroalbuminuria in hypertensive
recommended if u
mmHg. Use
ACR
but equivalence outside
therapy and risk of K
•
SGLT2
inhibitors improve glycaemic control and kidney outcomes (3×Ds: death, dia-
lysis, doubling of creatinine) in type
• Finerenone slows disease progression when added to
CKD
stages 3– 4. Used in addition to
• Statins reduce CV ris k. Uncl ear be nefit on dialysis but continue if tolerated.
Lupus nephritis
Systemic autoimmune disease with antibodies against nuclear components, eg
double- stranded (ds)
and tissue damage.
CNS
disease, cytopenia, and kidney disease. Nephropathy is common (50% in first
75
% overall). Can present as nephritis (p
year,
Clinical. Antibody profile:
cificity of
if u
II
75– 100
ACR
% and titres correlate with disease activity. Consider biopsy
>30, u
PCR
>50. Tre at me nt Depends on histological class. Classes I and
show mild changes with little risk of kidney disease progression:
nephroprotection and hydroxychloroquine for extrarenal disease. Classes
quire immunosuppression: mycophenolate, glucocorticoids, cyclophosphamide,
rituximab, belimumab. Ofatumumab may oer more
- associated vasculitis
Occurs with or without specificity for proteinase 3 (
Presentation Usually >60yrs, 20% of kidney biopsies >80yrs. Lethargy, fever, my-
SOB
algia, anorexia,
Clinical +
(‘pauci- immune’), alveolar haemorrhage.
, haemoptysis. Ask: 'When did you last feel well?' Diagnosis
ANCA
+ biopsy: rapidly progressive GN (p
cyclophosphamide/ rituximab. Benefit of plasma exchange is not clear: no reduction
in death or end- stage kidney disease in a randomized trial
receptor inhibitor) has shown non- inferiority to oral steroids.
Myeloma (p
366
)
Kidney disease in up to
kidney’), deposition of
renal tract infection due to immunoparesis.
for hypercalcaemia (e
(plasma exchange, large pore haemodialysis) unproven over standard chemotherapy.
25– 40
% over
BP
and poor DM control ac-
ACR
298
). Regression at this level of disease is possible. Not de-
ACR
>30mg/ mmol (‘severely increased’). HbA1c of 53mmol/
ACE-
i/
ARB
ACR
for CV and nephroprotection above BP con-
DM
. (Less clear benefit in normotensive DM but
>30mg/ mmol.) No head- to- head studies of
DM
. If cough with
+
. No benefit for direct renin inhibitors above
2
DM. Risk of (euglycaemic)
SGLT2
inhibitors. CI: hyperkalaemia.
DNA
. Deposition of antibody complexes causes inflammation
3– 30mg/ mmol (‘moderately
. Screen annually.
ACE-
i, switch to
ACE
ARB.
- i/
ACE-
i/
ARB
No benefit to dual
ACE-
i/
ARB
DKA
in type 1
ARB
DM.
in type 2 DM with
CVD
in DM
.
Presentation Rash, photosensitivity, ulcers, arthritis, serositis,
306
ANA
) or nephrosis (p
is sensitive but not specific. Anti- ds
B
- cell depletion than rituximab.
(AAV)
PR3
) and myeloperoxidase (
307
) without immune deposits
308
). Diagnosis
DNA
has a spe-
ACE-
i/
ARB
III– V
for
re-
MPO
Tre at me nt High- dose glucocorticoids plus
(PEXIVAS)
. Avacopan (C5a
40
%: tubular obstruction due to light chain casts (‘myeloma
I
g/ light chains in glomerulus (proteinuria), hypercalcaemia,
Tre at me nt Hydration, bisphosphonates
GFR
≥30), anti- myeloma chemotherapy. Light chain removal
).
Соседние файлы в папке Библиотека им академика М.И. Перельмана