What a Rheumatologists needs to know

about Nephrology

Dr Louise Moist

University of Western Ontario

Louise/moist@lhsc.on.ca

May 2014

• Advisory board Amgen, Leo Pharma, Roche

Disclosures

• 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

Abnormalities in Uremia

“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

Patient Subsets

Population

vs.

Patient

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

Drug Use in CKD

Drug use in CKD

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

Pain Control in CKD

Metabolic Bone DiseASE

Renal Osteodystrophy

• 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

Thank You!