What a Rheumatologists needs to know about...
Transcript of What a Rheumatologists needs to know about...
What a Rheumatologists needs to know
about Nephrology
Dr Louise Moist
University of Western Ontario
Louise/[email protected]
May 2014
• Update in recent trends in nephrology pertinent to the
rheumatologists in:
• Proteinuria/eGFR
• Lupus nephritis
• Gout in CKD
• Pain control in CKD
• Drugs in CKD
3
Learning Objectives
Kidney Disease 101
Damage
– Microalbuminuria is
a marker of
vascular/
endothelial damage
– Microalbuminuria
is a risk factor CVD
and CKD
Function
– Measure Cr
– Interpret with age,
sex, weight
– eGFR
– If abnormal consider
other kidney function
– Lytes, Ca, Phos,
Hb,acid base,
clearance (urea)
Rate
per
1,0
00 P
atient Y
ears
Hemmelgarn et.al. JAMA. 2010;303(5):423-429
Proteinuria predicts progression to ESRD > than
Creatinine
100x > risk of Dialysis
Rate
per
1,0
00 P
atient Y
ears
Proteinuria predicts death >creatinine
Hemmelgarn et.al. JAMA. 2010;303(5):423-429
Almost 10X > risk
When you see this...
Think this...
High albumin to creatinine ratio Or proteinuria on dip stick
HIGH CVD RISK
KEY POINT
> 90 60-89 30-59 15-29 <15
2 3 4 5 1 Stage
Description
GFR(mL/min/1.73m2)
Kidney Failure Severe
GFR Moderate GFR Kidney
damage with mild GFR
Kidney damage
with normal or GFR
Endstage Kidney Disease (ESKD)
= Dialysis or Transplantation
Stages of CKD GFR
0
10
20
30
40
50
60
70
80
90
15-29 30-59 60-89 90+
Estimated GFR (ml/min/1.73 m2)
Pro
port
ion o
f popula
tion (
%)
Hypertension* Hemoglobin < 12.0 g/dL
Unable to walk 1/4 mile Serum albumin < 3.5 g/dL
Serum calcium < 8.5 mg/dL Serum phosphorus > 4.5 mg/dL
*>140/90 or antihypertensive medication p-trend < 0.001 for each abnormality
“Uremia” & the Uremic Toxin
PTH
(9000 daltons)
Intracellular Ca2+
Alters/mitochondrial pathways/ ATP generation
Brain
Pancreas Myocardium Platelets Glucose
intolerance
Soft tissue calcification
Membrane
permeability &
integrity
abN phospholipid
turnover
Protein
catabolism
When you see this...
Think this...
Creatinine 145 umol/L eGFR == 35ml/min consistent with stage 3 CKD
HIGH CVD RISK
Impaired Immunity
Early CKD: altered cellular & humoral immunity
Alterations in PMN leukocytes – CHO metab, ATP generation, endothelial cell
adherance, ROS generation
– Impaired chemotaxis, phagocytosis, intracellular bacterial killing
Moderate lymphocytoepenia (circulating T cells)
Interferon production
Pt more susceptible to infections e.g. T.B., bacteremias, cancers, response to Hep B vaccinations
Mortality: The Facts
Stages 1-4 – Risk of death from CVD >>> renal disease
– 40% of patients with CKD will have CVD related death
– Approximately: Each 10 umol/L SCr
• 39% mortality
• 59% CVD related death
• Normotensive patients with MI
Mortality: Stage 5
Cardiac events in ESRD 3.5-50 times GP
Annual mortality on dialysis 15-20%
Cardiac causes of death 45%
Post MI – 1 year mortality = 59%
– 5 year mortality =90%
CKD Management
Reduce CKD progression – BP control
– Regression of proteinuria
– Use of ACEI/ARB
– Smoking cessation
Cardiovascular risk reduction – Depends on stage of CKD
Nephrology vs Rheumatology
• Experienced, dedicated, committed Dr.
• Stage 4 CKD for sure
• Management of CVS risk s
• Comanagement
26 yo
Creat 260 eGFR 30 (?),protein 2 g24 h, unwell
Anti dna 800, rash, leukopenia,
Biopsy Class IV LN
Steroids
MMF or Cyclophosphamide
MS LN ( Lupus nephritis)
1. Assuming Cyclophosphamide is the gold standard
Common Mistakes in Treating Lupus
Am J Kidney Dis. 63(4):667-676 2014
Appel, et al., JASN, 2009; Isenberg, et al, Rheumatol, 2010
Black, H
ispan
ic, Mixe
d
•The ALMS trial did not achieve its primary endpoint
•ALMS was NOT a non-inferiority trial
•However MMF has increasingly become the SOC
MMF vs CYC for LN-Results of the ALMS Trial
Rovin et al., CJASN, 2012
MMF vs CYC for SEVERE LN Defined as LN presenting with renal insufficiency
• decrease the frequency of lupus flare
• improves kidney outcomes
• increased probability of remission in membranous nephritis treated with MMF when combined with hydroxychloroquine
• lowers probability of decrease in kidney function if used prior to the onset of lupus nephritis
• probability of receiving an antimalarial agent is only 50%
if their primary lupus physician is a nephrologist
3.
Common Mistakes in Treating Lupus
Am J Kidney Dis. 63(4):667-676 2014
NOT USING ANTIMALARIAL AGENTS ROUTINELY
• ACR recommends using urinary sediment for assessing response
• improvement defined as changing from active urinary sediment to inactive
urinary sediment (5 RBCs, 5 WBC, and noRBCs and no WBCs
• the quantity of cells or casts is influenced by the duration of centrifuge time
• mesangial proliferation (class II nephritis) can be associated with RBCs and
casts and these lesions do not require immunosuppressive
• using urinary sediment for response criteria can be misleading and
result in unnecessary use of potentially toxic therapies.
4. USING URINARY SEDIMENT FOR RESPONSE CRITERIA
Common Mistakes in Treating Lupus
Am J Kidney Dis. 63(4):667-676 2014
• CKD 4 or 5 D , a renal-limited flare might not warrant
immunosuppressive tx
• significant scarring in the kidney
• very little or no benefit from another course of therapy.
• immunotherapy guided by extrarenal manifestations.
• dialysis pt immunosuppressive dose should be minimized high risk of
infection.
NOT REDUCING OR MINIMIZING IMMUNOSUPPRESSIVE
EXPOSURE IN PATIENTS WITH ADVANCED KIDNEY
DISEASE
Common Mistakes in Treating Lupus
Am J Kidney Dis. 63(4):667-676
• Abnormal renal function
• Careful in young people Creat 50 increases to 90
• Proteinurea
• 1 gram may be masked if on ACEI ARB
• Consider if marked change in presentation
• Fibrosis scarring vs active disease
• Risk vs Benefit
WHEN to do A BIOPSY
Common Mistakes in Treating Lupus
Case -Clinical History
51 y.o. female SLE presented with microscopic hematuria
creatinine 80 to 115 mol/L over 2 years
• Positive ANA (1:640) with anti-Smith antibodies
• C3 level low normal C4 level
• UA: large blood, 1+ protein, and 20 RBCs/ HPF,
• Urine protein-creatinine ratio was 0.5
• positive lupus anticoagulant
What additional information would
you like?
Creat 120 eGFR 60 ,protein .5g24 h
• 2mo later returns creat 190, alb/cr 50
6 months later
MMF 1250 gm bid prednisone 15mg ,ramipril 5mg, Plaquenil
MS LN ( Lupus nephritis)
Rule out other causes of rise in creatinine
• Volume status
• Drugs NSIADs, ACEI, ARB,DRI
• Predisone ( urea)
• Septra
• ACEi ARB DRI
Repeat Cr follow up
Lupus nephritis
Pregnancy
• Education risks
• Remission 6mo
• Lupus anticoaulant before BCP
• Switch to azothioprine and stable
• Off ramipril
• Stay on hydroxychloroqine
• Prognosis based on renal function Cr 160
• Co manage high risk OB
Lupus nephritis
MR Tophi
65 yo HT, Creat 162 eGFR 42ml/min
Ramipril, HcT, ASA 81mg. Statin
Boys weekend ( moose meat, booze)
Acute gout, treated wih NSAID,
3 days later to emerg Creat 640
uric acid 800
Gout in CKD
Cause of AKI?
ACEI / NSAID combo
dehydration
Time to recovery
• Renal mass
Need for prophylaxis?
dose of Allopurinol
exacerbation of gout
Mr Tophi
Treatment
• NSAIDS
• Colchicine
• 1-2 0.6mg per day
• Steroids
Prevention
• Colchicine • 20% excreted kidneys
• neuropathy, myopathy, BM
• No if eGFR < 15ml
• 15-30 ml q 3days
• Caution statins
• Allopurinol • Dose reductions?
• Slow titration
• Uloric
• No role for uricosurics < 60ml
Gout in CKD
Victim
Gentamycin Acyclovir Indinavir
Sodium phosphate Pamidronate
Cisplatin Hetastarch
Calcineurin inhibitors Gold
NSAIDs Beta-lactams
Accessory
Disruption of Functions NSAIDs
Thiazide diuretics TMP-SMX
Prolonged Effects Benzodiazapines
Methotrexate Glyburide
Drugs In CKD and Rheumatology
Septra and CKD
Dose-response • SS TMP-SMX, OR = 3.4 (1.6 – 7.4)
• DS TMP-SMX, OR = 6.6 (3.5 – 12.6)
Hyperkalemia • 14% of patients had electrolyte testing after Rx
• Absolute risk of hyperkalemia = 6.9/1000 TMP-SMX Rx
Mortality • 26/189 (14%) died during admission
• Absolute risk of death (21 day) = 26.2/1000 TMP-SMX Rx
Slide courtesy of Matt Weir
. Modified WHO analgesic ladder in patients with chronic kidney
Parmar MS, Parmar KS. 2013 [v3; ref status: indexed, http://f1000r.es/10f] F1000Research 2013, 2:28 (doi: 10.12688/f1000research.2-28.v3)
Pain Control and CKD
• hip fracture risk women > 65 • eGFR of 45 to 59 mL/minute (HR 1.57, 95% CI 0.89-2.76)
• eGFR <45 mL/minute (HR 2.32, 95% CI 1.15-4.68)
• FRAX no eGFR
• DXA measures areal BMD, rather than volumetric BMD • cannot distinguish cortical and trabecular bone
• cannot assess bone microarchitecture/ bone turnover
• DXA eGFR > 30 hyperparathyroidism, hyperPO4 • Oral bisphosphonate
• DXA <30 is not routinely performed • Only under special circumsances
Diagnosis of Osteoporosis in CKD
Summary
• CKD secondary to factors related to Rheum is multifactorial and multidisciplinaery
• Each stage has associated multi-system morbidities
• Management of the Rheum Dx
• Prevent progression with aggressive BP and proteinuria control
• Prevent CVD using CKD specific risk factor modification