Transcript The Patient with Elevated Creatinine

Approach to Renal
Disorders
AIMGP Seminar
Revised by Nick Hariton November 2006
Objectives



To identify appropriate strategies for
investigation of the patient with kidney disease
To discuss interventions that may alter the
course of disease
To discuss indications for referral to a
nephrologist
Guidelines



Elevated Serum creatinine: recommendations
for management and referral. CMAJ 1999:
161:413-17
National Kidney Foundation: Kidney Disease
Outcomes Quality Initiative (NKF-KDOQI),
2002
Practice guidelines for Chronic Kidney Disease.
2003. Annals of Internal medicine. Vol. 139
Number 2.
Stages of Renal Failure
Stages of Renal Failure
GFR (cc/min)
Stage 1
>90
Stage 2 (Mild)
60-90
Stage 3 (Moderate)
30-59
Stage 4 (Severe)
15-29
Stage 5 (End-stage)
<15
Creatinine is an estimate of GFR
Cockcroft-Gault:
(140-age) x wt x 100 = GFR (cc/min)
72 x serum Cr
GFR (females) = GFR (males) x 0.85


MDRD

24 hour urine for creatinine
CASES: What is Considered an
ELEVATED Creatinine?
55 yo 70 kg male with Cr of 220:
GFR =37
moderate
75 yo 45kg female with Cr of 220:
GFR = 16
severe
75 yo 45kg female with Cr of 85:
GFR =40
moderate
75 yo 45kg female with Cr of 45:
GFR =76
mild
Workup of a decreased GFR

Approach

1. Identify chronicity (Acute vs chronic)

2. Identify the cause, especially reversible causes

3. Identify Indications for Referral to a Nephrologist

4. Initiate a cause specific management plan in a
multidisciplinary team.
Acute vs Chronic Renal Failure
ACUTE
- Fever
- Hypovolemia
- Sepsis
- New hypertension
- Recent nephrotoxins
- No hypocalcemia
- No hyperphosphatemia
- No anemia
CHRONIC
- previous confirmed
nephropathy
- Already diminished CrCl
- Atrophic kidneys
(<10cm on U/S)
- Normochromic
normocytic anemia
- Hypocalcemia
- Hyperphosphatemia
Abdominal Imaging

Normal size kidneys in chronic kidney disease
Diabetes
 Polycystic kidney disease
 Myeloma Kidney
 Amyloidosis
 HIV Nephropathy

Underlying Cause
CHRONIC
KIDNEY DISEASE
PRE-RENAL
RENAL
POST-RENAL
GLOMERULAR
INTERSTITIAL
VASCULAR
Pre-Renal Disease

Medications:




Renal Artery Stenosis
Decrease effective circulating volume




NSAID
Diuretic
Congestive heart failure
Cirrhosis
Hypovolemia (losses or decreased intake)
Normal urine sediment, decreased urine [na+],
increased BUN:Cr
Post-Renal Disease

Intraluminal obstruction:


Nephrolithiasis
Luminal obstruction
Transitional cell carcinoma
 Severe BPH


Extraluminal obstruction
Retroperitoneal fibrosis
 Lymphadenopathy (lymphoma)
 Mass

Glomerular Disease

Active Sediment (RBC casts, hematuria)
IgA Nephropathy
 Post-infectious GN
 Autoimmune disease and vasculitis
 Chronic hepatitis and HIV


Nephrotic Syndrome (bland sediment, >3g/day
proteinuria)
Primary and secondary causes
 DIABETES

Interstitial Disease






Polycystic Kidney Disease
Chronic infectious pyelonephritis
Allergic interstitial nephritis
Autoimmune interstitial nephritis
Reflux nephropathy
Myeloma Kidney
Vascular Disease

Large-sized Arteries


Renal artery stenosis
Medium-sized Arteries
HYPERTENSIVE NEPHROSCLEROSIS
 Vasculitis


Arterioles


Microangiopathies (scleroderma, HUS/TTP,
cyclosporine)
Venous thrombosis
History and Physical Exam

signs or symptoms of
underlying disorder: i.e. volume status, flank pain,
obstruction, diabetes, hypertension, vasculitis
 altered kidney function: urine output, urine
discoloration, edema
 renal failure: anorexia, vomiting, altered mental
status, HTN


medications: NSAID, ACEI, analgesics,
aminoglycosides, contrast, Chinese herbs
Laboratory Investigations

Required:






Estimation of GFR
Urinalysis
Albumin:Creatinine Ratio
Renal Imaging
CBC, Electrolytes, Calcium, Phosphate, Bicarb, Albumin
Potentially useful:






24-hour Urine protein
Fasting Glucose
Serum / Urine Protein Electrophoresis
HIV and Hepatitis serology
Autoimmune serologies
MR Angiography
UptoDate
Renal Biopsy

Should be considered:

Ff noninvasive tests have failed to establish a
diagnosis in a patient with:
Nephrotic syndrome (except in DM or established
amyloid)
 Non-nephrotic proteinuria if associated with renal
dysfunction
 Lupus nephritis (for dx and staging)
 Acute nephritic syndrome
 Unexplained acute/ subacute renal failure


To direct and evaluate effectiveness of therapy
Management of Renal Disease

Treatment of Reversible Causes

Preventing or Slowing Progression

Treating and Preventing the Complications

Identifying Individuals Requiring Renal
Replacement Therapy
Slowing Progression
Hypertension

ACE inhibitors preferred because:
More potent antiproteinuric effect, especially in nondiabetics
 Large body of evidence from RCTs (in diabetics
and non-diabetics)
 RRR 30% for progression to ESRD


Benefit persists in severe kidney disease
Management of Complications








Coronary artery disease
Anemia
Calcium and phosphate homeostasis
Renal osteodystrophy
Platelet dysfunction
Fluid overload
Acidosis and hyperkalemia
Decreased drug clearance
Referral to Nephrologist


Late referral (< 12 months pre dialysis) is common
Survey of Ontario Family MDs:




84% would not refer with creat 120-150 (>50% loss of GFR)
28% would not refer with creat 150-300
almost all would refer with creat>300
Consequences of referral shortly before dialysis:





more complications
longer hospitalization to initiate dialysis
more difficulty with initiation of dialysis
worse survival!
Better outcomes with early multidisciplinary care
CMAJ 1999: 161:413-17
Canadian Guidelines





Renal replacement therapy is NOT rationed (i.e.
everyone should be considered)
Reversible causes should be sought at diagnosis
At least 1 year is required to prepare for dialysis
Refer, at the latest, at Cr clearance of 30 ml/min, or Cr
of 300
But…there are probably not enough nephrologists/
clinics to meet this demand

Adequate communication with the Nephrologist will allow
proper stratification of patients
CMAJ 1999: 161:413-17
For AIMGP Clinic


It is reasonable to follow stable renal failure patients,
and work up and manage appropriately
Refer to nephrology when:



Cr >300 or Cr clearance <30 ml/min
Renal biopsy indicated
Indicators of aggressive disease are present:






Rapid decline in creatinine
homeostatic derangement i.e. acidosis, volume overload, high K
high protein excretion
Difficult to control BP
low HDL
black race
In Summary
Appoach To Proteinuria

Normal Protein Elimination:
< 150mg / day protein
 < 30mg / day albumin


Classification of Proteinuria
Transient
 Orthostatic
 Persistant

Glomerular barrier
tubule
• Normally, the larger proteins are excluded at
the glomerular barrier
• Smaller proteins can pass, but are mostly
reabsorbed
Mechanisms of Proteinuria

Glomerular Dysfunction
Leakage of large proteins through glomerular
membrane and podocytes
 Transient (epinephrine and AII mediated)

Fever
 Exercise
 Congestive Heart Failure


Persistant

Glomerular Disease
Leaky Glomerular barrier
tubule
•Large proteins are able to pass by the
abnormal glomerular barrier
Mechanisms of Proteinuria

Tubular Dysfunction
Inability of renal tubules to reabsorb small filtered
proteins
 Specific transporter dysfunction



Eg Fanconi’s syndrome
Generalized tubular dysfunction
Progressive chronic renal failure
 Interstitial Disease

tubule
Malfunctioning tubules unable to reabsorb the smaller
proteins filtered at the glomerulus
Mechanisms of Proteinuria

Increased filtered protein load

Overwhelms ability of kidney to reabsorb protein

Increased GFR (mild proteinuria)


Pregnancy, fever
Increased filtered protein

Myeloma, MGUS
Glomerular barrier
tubule
• Filtered load of proteins exceeds the tubular
reabsorption rate (similar to glucosuria in
hyperglycemia)
Diagnostic Approach

Step 1






Clinical Assessment (History and Physical) and examination
of urinary sediment
History: urinary symptoms, infections, rash, risk factors for HIV
and hepatitis
Pmhx: Cancer, CHF, HTN, CTD, DM
FHx: Alports, Fabry’s
Drugs: NSAIDS, Gold, Heroin
Physical exam: vitals, JVP, peripheral edema, ascites, rash, joint
swellings
Diagnostic Approach

Rule out transient proteinuria with repeat
urinalysis:

Fever, exercise, UTI

In young patients (age < 30) perform a split
urine collection (upright and supine) to exclude
orthostatic proteinuria

If the above investigations are negative - STOP
Diagnostic Approach

Persistant proteinuria not due to a known underlying
cause (eg CHF or diabetes) requires further
investigation for glomerular and interstitial disease:








24h urine for protein or urine albumin:creatinine ratio
Serum creatinine and estimation of GFR
CBC, electrolyes, Fasting blood sugar
Serum and urine protein electrophoresis
Serology: Hep B, Hep C, HIV, ASOT, VDRL
ANA, Rheum factor, C3/C4, ANCA
Renal Imaging (eg ultrasound)
Malignancy screen
Renal Biopsy


Indications for renal biopsy:
Diagnosis unclear and
Persistant proteinuria with > 3g / day
 Increasing proteinuria
 Declining GFR


Prognosis and management

Eg staging SLE nephritis
Summary

Asymptomatic proteinuria is a common problem

Initial investigations are targeted to rule out
transient, self-limited conditions and benign
orthostatic proteinuria

Persistent proteinuria, particularly nephrotic
range or associated with declining GFR, requires
further investigation
Conclusions

When evaluating a patient with a renal disorder:
Identify and treat reversible causes of renal failure
 Initiate management to slow the decline in renal
function
 Manage coexisting conditions
 Have clear indications for when to refer to
nephrology subspecialists
 Organize an approach to asymptomatic proteinuria
