Transcript Clinical Case Conference

Clinical Case Conference
REBIN TITUS
Presenting history
 71-year-old Caucasian female with past medical
history notable for hypertension and arthritis,
transferred from Roswell secondary to acute renal
failure
 She was of her usual state of health up until 4
months ago, when she developed swelling of her
hands and feet.
 She reports that she was gardening one day 4
months ago and the next day she woke up with joint
pain, swelling of the bilateral upper and lower
extremities especially the hands, wrist and ankles.
Presenting history
 Since then, she has been admitted to the hospital
numerous times for the same complaints
 Patient still complains of pain and swelling in
multiple joints on day of presentation and states that
her swelling waxes and wanes
 Since April, she has had an extensive workup, and
was being followed by an internist, nephrologist and
rheumatologist.
 She also reports some difficulty breathing, along
with difficulty swallowing.
Past Medical History
 Hypertension.
 Polyarthritis.
 Diverticulosis with history of diverticulitis
Over past 4 months:
 Acute renal failure.
 Anemia of unknown etiology.
 Dysphagia.
 Dyspnea
 Worsening hypertension.
Past Surgical History
 Bilateral knee replacements.
 Right shoulder surgery.
 Colon resection.
History (contd.)
 Social History: Patient smoked ½ pack per day for
20+ years, quit 4 years ago, has not started back.
Patient is a social drinker, states she drinks 3-4
alcoholic beverages a week. No use of illicit drugs.
Lives in Roswell
 Family History: Positive for lymphoma in father.
Medications
 Alendronate
 Amlodipine
 Epoetin
 Metoprolol
 Morphine
 Omeprazole
 Zofran
 Prednisone 15 mg
 Ambien.
PE
 Vitals: Temp: 95.6; BP 162/90; HR 83, RR 16; O2
sat 93% on room air.
 Gen appearance: Comfortable, in no distress
 HEENT: PERRLA, normal conjunctivae, moist
MM, eyes
 Neck: Supple, no lymphadenopathy
 Lungs: CTAB
 CVS: S1, S2, RRR, no M/R/G
 Abd: Soft, BS +, NT/ND
 Ext: No C/C trace edema around ankles
 Mildly edematous joints of both hands with ulnar
deviation, slighlty tender with taut skin
PE (contd.
Labs (8/2)
 CBC : WBC 12.5 , H/H 10.3 and 30.8, platelets 126K.
 BMP: Sodium 136, potassium 4.3, chloride 104, C02
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21, glucose 95, BUN 79, creatinine 4.3, calcium 8.3.
LFT: ALT 28, AST 31. Total bilirubin 0.9.
Iron studies: Iron level 53. TIBC 233. Transferrin 23.
Ferritin level 1,727.
TSH 2.87. Free T4 1.29.
Spot Urine with protein 123, creat 47. UA positive for
moderate blood, sp gravity 1.009
Other labs from Roswell
 ASO negative. RF negative.
 ANA negative. Ds-DNA pending.
 RNP pending. Scleroderma antibody negative
along with reports from the nephrologist of pANCA and c-ANCA negative.
 Creatinine on 6-15-09 at 0.8 with subsequent rise
approximately 2.5 to 3.0 without return to
baseline.
Admission day # 2,3,4
 Doing well, good urine output, no complaints
 Continued on home meds
 Creatinine continuing to trend upwards: 4.5, 4.6,
4.9, BUN in the 70-80’s
 BP also trending up
Admission day # 5
 Continues to do well
 Producing good urine output
 BP uncontrolled, systolics in the 180-200’s
 Creatinine now up to 5.5, BUN 95, GFR 10
 Biopsy scheduled
Admission day # 6, 7
 Biopsy results suspicious for thrombotic
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microangiopathy, suspicion for scleroderma
Started on low dose captopril
Low dose steroids stopped
Creatinine continues to rise, rapidly progressing,
now up to 6.7, BUN 116, GFR 8
BP continues to be uncontrolled
Pt now is tired and fatigued, urine output decreased
Biopsy
 Thrombotic microangiopathy
 The histologic appearance is consistent either with malignant
hypertension, scleroderma renal crisis, hemolytic uremic
syndrome or cancer chemotherapy
 Moderate increase of mesangial matrix. The interlobular
arteries show moderate narrowing. Minimal lymphocytic
infiltration is seen in the interstitial tissue. Less than 10% of
renal parenchyma is lost by tubular loss and atrophy and
interstitial fibrosis.
 IgA, IgG, IgM, C1q, C3, C4 and albumin are negative. No
immunoglobulins, complements, albumin or fibrinogen seen
along the tubular basement membrane or blood vessel wall.
Marked thickening of vessel wall with
narrowed lumen
Thrombi in capillary loops and arteriole
Thrombi in capillary loops and arteriole
Loss of parenchyma by interstitial fibrosis and tubular atrophy
Admission day # 7,8
 Increasing doses of captopril, upto 50 mg tid
 BP some better 150-190’s systolics
 Now being treated as a scleroderma renal crisis
 Creatinine continues to rise 7.4, 8.2; BUN 115, 117,
Admission day # 9,10
 Creatinine 9, BUN 117, K 5.4, with some altered
mentation, also some nausea, low appetite
 Decision made to dialyze secondary to uremic
symptoms
 Tunnel catheter placed
 BP now under good ctrl
Admission day # 11,12
 Patient tolerated dialysis well, improved
 Creatinine down to 5.9, BUN 60, other lytes normal
 BP well controlled on captopril
 Induction for dialysis
Admission day #13, 14, 15
 Continues hemodialysis daily
 Creatinine down to 5.1, 5.5
 Tunnel catheter placed
 Set up for routine hemodialysis in Roswell
 Discharged home
Scleroderma renal crisis
 Abrupt onset of moderate to severe hypertension
 Urine sediment that is normal or reveals only mild
proteinuria with few cells or casts
 Progressive renal failure
 Severe and life-threatening
Scleroderma renal crisis
 Can develop in approximately 10 to 20 percent of
patients with the diffuse cutaneous form of systemic
sclerosis and much less frequently in limited
cutaneous systemic sclerosis.
 Despite the widespread use of ACE inhibitors for the
treatment of scleroderma renal crisis, morbidity and
mortality remain high.
Prevalence
 Approximately one-half of scleroderma patients
show some evidence of renal involvement, such as
proteinuria, a mild elevation in the creatinine
concentration, and/or hypertension
 Scleroderma renal crisis (SRC) develops in up to 20
percent of patients with diffuse cutaneous systemic
sclerosis, although its incidence appears to be
declining
Risk factors
 Diffuse skin involvement
 Glucocorticoid use
 Presence of certain autoantibodies like anti-RNA
polymerase antibodies .
Clinical Features
 Occurs within the first five years of the onset of the
disease. In one series, renal crisis occurred at a
median duration of 7.5 months from the onset of the
disease. In some cases, SRC is the initial
manifestation of systemic sclerosis.
Clinical features
 Acute renal failure, usually in the absence of previous kidney
disease.
 Abrupt onset of moderate to marked hypertension, often
accompanied by manifestations of malignant hypertension, such
as hypertensive retinopathy and hypertensive encephalopathy.
 In approximately 10 percent of patients, SRC occurs in the
presence of normal blood pressure. However, some of these
patients have blood pressures that are still higher than the
patient's baseline. These patients tend to have a worse renal
outcome and higher mortality than patients with SRC who are
hypertensive.
 The urine sediment is usually normal or reveals only mild
proteinuria with few cells or casts. Nephrotic range proteinuria is
uncommon.
Pathology
Pathological hallmarks of scleroderma or systemic
sclerosis:
 Uncontrolled accumulation of collagen
 Widespread vascular lesions characterized by
thickening of the vascular wall and narrowing of the
vascular lumen.
Pathology
 The primary histopathologic changes in the kidney are
localized in the small arcuate and interlobular arteries and the
glomeruli. The characteristic finding is intimal proliferation
and thickening that leads to narrowing and obliteration of the
vascular lumen, with concentric "onion-skin" hypertrophy.
 SRC is a thrombotic microangiopathy similar to malignant
nephrosclerosis, TTP/HUS, radiation nephritis, chronic
transplantation rejection, and the antiphospholipid antibody
syndrome.
 Because of the similar renal histologic findings, renal biopsy
does NOT definitively establish the diagnosis of SRC.
Histology
Light micrograph showing fibrinoid necrosis in the preglomerular
afferent arteriole (arrow) in scleroderma renal crisis. The normal muscle
layer of the media has been replaced by the fibrinoid material
Other features of SRC to make diagnosis
 Digital tip pitting and scarring, and nailfold
microvascular changes with capillary dilatation
 Evidence of gastrointestinal involvement (such as
esophageal or small bowel dysmotility);
 interstitial lung disease or pulmonary hypertension
 The presence of serum autoantibodies against RNA
polymerase. By contrast, the presence of anticentromere antibodies appears to be protective
against the development of SRC.
Prevention
 No prospective studies that demonstrate that the avoidance and/or
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administration of any agent lowers the incidence or severity of SRC have been
performed.
ACE Inhibitors: There is no clear evidence of a preventive effect of ACE
inhibitors among patients with systemic sclerosis
Retrospective and case-control studies have largely found neither benefit nor
harm with ACE inhibitors related to the development of SRC
A multicenter randomized, double-blind, placebo-controlled study of 210
patients evaluated the efficacy of daily quinapril(80 mg/day or the maximum
tolerated dosage) for the prevention of vascular damage in systemic sclerosis.
At two to three years, quinapril did not affect the occurrence of vascular
complications, such as Raynaud phenomenon or ischemic digital ulcers, and
had no effect on renal function.
Avoidance of glucocorticoids
Treatment
 The mainstay of therapy is effective and prompt blood
pressure control, which improves or stabilizes renal
function in up to 70 percent of cases and improves patient
survival (survival at one year of 80 percent). The success
with antihypertensive therapy is dependent upon its
initiation before irreversible renal damage has occurred.
 The optimal class of antihypertensive agents is ACE
inhibitors. Compared to other antihypertensive agents, a
number of nonrandomized, uncontrolled retrospective and
prospective studies have shown that the ACE inhibitors are
associated with greater antihypertensive efficacy, better
preservation of renal function, and improved survival in
patients with scleroderma renal crisis
Initial goals of therapy
 Captopril has the advantages of rapid onset (peak
effect at 60 to 90 minutes) and short duration of
action, which permit rapid dose titration.
Intravenous enalaprilat is not routinely used.
 The principal goal of initial captopirl therapy is to
return the patient to his or her previous baseline
blood pressure within 72 hours
 If evidence of central nervous system involvement
like encephalopathy or papilledema, may add
intravenous nitroprusside
Outcomes
 Despite treatment with ACE inhibitors,
approximately 20 to 50 percent of patients with SRC
progress to end-stage renal disease.
 However, among patients with SRC who require
dialysis during the acute episode, an appreciable
proportion recover sufficient renal function to
discontinue dialysis
ACE Inhibitor studies
 A prospective observational cohort study study from Georgetown University
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reported patient outcomes in 145 patients with SRC who were continuously
treated with ACE inhibitors
28 patients (19 %) died at a mean of three months, 18 of whom required
dialysis.
55 patients (38 %) did not require dialysis. These patients had a mean peak
serum creatinine concentration of 3.8 mg/dL that fell to 1.8 at 7.1 years. Only
two had slow deterioration of renal function, requiring dialysis at four and six
years.
28 patients (19 %) required permanent dialysis.
34 patients (23 % overall, 43 % of all patients requiring early dialysis, and 55 %
of patients requiring early dialysis who did not die) were able to discontinue
dialysis after 2 to 18 months (mean eight months). The mean serum creatinine
was 2.7 mg/dL when dialysis was discontinued that fell to 2.2 mg/dL at 6.1
years.
In an earlier report from the same group cited above, there was no recovery of
renal function in patients not treated with ACE inhibitors
ACE Inhibitor studies
 In a retrospective single center study from London in 2007,
of 110 patients with SRC (mean blood pressure of 193/114
mmHg), 108 were treated with ACE inhibitors. ACE
inhibitor therapy was titrated to reduce the systolic blood
pressure by 20 mmHg per day. Dialysis was required in 72
patients (64 %), 24 of whom (33 %) recovered sufficient
renal function to discontinue dialysis. At three years, renal
function improved (mean 23 mL/min) among non-dialysisdependent patients. Approximately 40 percent of patients
required permanent dialysis. Overall patient survival at one
and five years was 82 and 59 percent, respectively, with the
poorest survival seen in those requiring dialysis.
Other therapies (not proven)
 Angiotensin II receptor blockers might be expected
to be effective, but the efficacy of these drugs has not
yet been established.
 Intravenous prostacyclin, which is believed to help
the microvascular lesion, has been administered at
the onset of hypertensive renal crisis based upon
anecdotal observations of benefit.
 Fish oil is sometimes prescribed in view of its
theoretically beneficial hemodynamic and
antiplatelet properties.
Mortality
 SRC is a potentially life-threatening complication. Prior to
the widespread use of ACE inhibitors, almost all patients
with significant renal involvement died within one year
(compared to a 35 percent cumulative seven-year survival
in all patients).
 Survival of patients with SRC treated with ACE inhibitors is
significantly better
 In a review of 110 patients with SRC, one-year patient
survival was 76 percent in patients treated with ACE
inhibitors compared to 15 percent in patients treated with
other drugs.
Summary
 As many as 50 percent of scleroderma patients have clinical
evidence of renal involvement, such as mild proteinuria,
elevated serum creatinine concentration, or hypertension
 SRC develops in up to 10 to 20 percent of patients with
diffuse cutaneous systemic sclerosis. It is characterized by
acute renal failure, abrupt onset of moderate to marked
hypertension, a normal urinalysis or a urine sediment with
only mild proteinuria and/or signs of microangiopathic
hemolytic anemia.
 The characteristic histologic finding in the kidney in SRC is
intimal proliferation and thickening that leads to narrowing
and obliteration of the vascular lumen, with concentric
"onion-skin" hypertrophy
Summary
 The diagnosis of SRC is based upon characteristic findings
which include new onset of blood pressure >150/85 mmHg
and progressive decline in renal function, although a few
patients are normotensive. Additional findings may include
microangiopathic hemolytic anemia and
thrombocytopenia, features of malignant hypertension,
new onset proteinuria or hematuria (excluding other
causes)
 SRC must be distinguished from other forms of thrombotic
microangiopathy, particularly TTP/HUS
 The principal goal of initial ACE Inhibitor (captopril)
therapy is to return the patient to his or her previous
baseline blood pressure within 72 hours
Thank you for your attention