Professional Documents
Culture Documents
Acute Renal Failure in Ambulatory Patients: The Role of Glomerular Pathology
Acute Renal Failure in Ambulatory Patients: The Role of Glomerular Pathology
Divisions of Nephrology & Pathology Drs. K. Jindal, K. Solez, B. Sis, Jindal, Solez, J. Bradley, S. Reddy Medical Grand Rounds February 27th, 2004
Acute Renal Failure in Non-hospitalized Patients NonHemodynamic Acute interstitial nephritis Glomerular disease Microangiopathic disorders
Objectives
Spectrum of glomerular diseases causing ARF Clinical cases Pathology Diagnosis Pathogenesis Treatment Research opportunities
Ms. R.J.
30 year old Caucasian female referred for assessment of Acute Renal Failure Past medical history unremarkable No regular medications Originally presented to her family physician complaining of continuous pain in her right ear
Ms. R.J.
Initially diagnosed with otitis media Treated with Septra DS 4 days later developed a macular rash on her hands, feet, shins and back The Septra was discontinued and the rash resolved within a few days Cr 76 umol/L umol/L
Ms. R.J.
One month later, returned to her family physician, this time complaining of diffuse arthralgias Prescribed voltaren prn Subsequently had some mild hematemesis hemoptysis Gastroscopy was ordered, found to be unremarkable
Ms. R.J.
However, a repeat assessment was done BP 120/78 Remainder of exam noncontributory Cr 340 umol/L umol/L Urea 33 mmol/L mmol/L Hgb 101 g/L HCO3- 19 mmol/L mmol/L
Ms. R.J.
U/A 3+ proteinuria, 3+ hematuria
No assessment or documentation of RBC casts
Ms. R.J.
ANA negative cANCA positive C3 1.17 (N 0.80 2.00) C4 0.28 (N 0.18 0.36) ASOT negative Cryoglobulins negative
Ms. R.J.
Summary 30 yo female with a rapid onset of acute renal failure associated with systemic arthralgias, middle ear involvement, arthralgias, cANCA positivity and an active urine sediment
Must rule out a rapidly proliferative GN
Ms. R.J.
Differential Diagnosis Pauci-immune GN (particularly PauciWegeners Ganulomatosis) Wegener Ganulomatosis) Immune complex GN (including postpostStrept GN) Anti-GBM AntiAlso consider
Acute Interstitial Nephritis (2O Septra or NSAIDS)
IF
IgG- Mild to moderate mesangial staining IgGIgA- Mild mesangial staining IgAIgM- Moderate mesangial staining IgMC3- Moderate mesangial staining C3C1q- Negative C1qKappa- Mild mesangial staining KappaLambda- Negative LambdaFibrin- Mild interstitial staining, single possible Fibringlomerular capillary thrombus Albumin- Mild hyaline droplet change in Albumintubular cytoplasm
IgA
IgM IgM
Kappa
C3
IgA Kappa
C3 Fibrin
Diagnosis:
Renal Biopsy: Crescentic and necrotizing immune complex glomerulonephritis. glomerulonephritis.
Mrs. J. K.
RFR: ARF CC: Edema from leg to abdomen for one month HPI:
84 yr old female PMHx:
Osteoporosis GERD
Mrs. J. K
HPI:
One month history of increasing edema from legs and now up to her abdomen. Seen by GP at onset of symptoms and started on Lasix 40mg TID and Aldactone 25 mg daily.
Mrs. J. K
HPI contd: cont
No improvement on edema, if anything getting worse. No previous history of MI or CHF. No history of chest pain prior to onset of symptoms. No History of Orthopnea or PND, but nocturia times 4.
Mrs. J. K
HPI contd: cont
No history of Liver disease, jaundice, hepatitis or ETOH abuse in the past. No history of dysuria, frequecy or urgency. No history of gross hematuria.
Mrs. J. K
HPI contd: cont
No exposure to contrast dye, NSAIDS, or recent antibiotic use. No fever, weight loss night sweats or chills. No previous history of malignancy
Mrs. J. K
Medications:
Lasix 40mg PO TID Aldactone 25 mg PO daily Didrocal Kit
Allergies:
None
Examination
Vitals:
P=80, BP = 144/80, RR = 16, T = 36.2, 96% on RA, JVP @ 3 cm ASA
Laboratory Data
Hgb WBC Platelets Sodium Potassium Chloride CO2 BUN Creatinine 139 6.3 434 118 4.2 83 24 18.1 181 (83) AST ALT ALP T. Protein Albumin Osmolality T. Cholesterol FBS 30 22 75 51 20 259 7.38 5.0
Chest and CVS unremarkable No Hepatosplenomegaly 3+ pitting edema from legs to sacrum. No lymphadenopathy or rash noted.
Laboratory Data
Urinalysis:
3+protein, Hb 3+, Leukocytes negative, occassional WBC, 1-5 RBC. 1-
Laboratory Data
SPE = decrease albumin Hep B and C serology negative. C3 = 1.43 (N 0.80 2.00) C4 = 0.2 (N 0.18 0.36)
Protein: Creatinine
571
ANCA Negative
Working Diagnosis
Differential Diagnosis
Minimal change disease with ATN or AIN
IF
IgG-Negative high background. IgGIgA- Negative high background. IgAIgM- Trace mesangial close to negative. IgMC3- Patchy moderate Bowmans capsule and C3Bowman tubular basement membrane,doubtful significance. C1q- Negative. C1qKappa- Negative high background. KappaLambda- Negative high background. LambdaFibrin- Moderate interstitial. FibrinAlbumin-Moderate background staining with Albuminaccentuation of Bowmans capsule and tubular Bowman basement membranes,doubtful significance.
10
Diagnosis: Renal Biopsy: Acute Tubular Injury And Regeneration. Arteriosclerotic Vascular Disease, Moderate. Most Likely Cause of Nephrotic Syndrome is Minimal Change Disease Although Focal Glomerular Sclerosis Cannot Be Completely Excluded.
RPGN
Loss of renal function over weeks Crescent formation Pauci immune Anti-GBM antibody AntiImmune complex
11
Casts are aggregates of cells & protein formed within renal tubules Cells in casts come from the kidney, not renal pelvis, ureters, or bladder RBC casts generally are a sign of glomerular inflammation
RPGN Diagnosis
Anti-GBM antibody AntiANCA ANA, anti-DNA antiASOT Complements RENAL PATHOLOGY
Pathogenesis of ARF
RPGN Decreased effective filtration Tubulointerstitial disease Fibrosis
12
Treatment
Anti-GBM antibody disease AntiEarly diagnosis Methylprednisolone 7-15 mg/kg/day x 3 days Oral Prednisone Plasma exchange for 14 days Cyclophosphamide for 8 weeks
13
Treatment
Pauci-immune crescentic RPGN PauciMethylprednisolone 7-15 mg/kg/day x 3 days Prednisone for 612 months 6 Cyclophosphamide until remission Azathioprine or cyclophosphamide 1218 12 months
Treatment
Minimal Change Disease with ARF
Prednisone 60 mg/m2/day for 4-6 weeks 440 mg/m2 every other day in responders for 4-6 weeks Cyclophosphamide in non-responders non-
Case #2 Mrs. J. K
Started on Prednisone 40 mg/day Two weeks later:
Creatinine decreased to 91 Protein:Creatinine <19 Anasarca resolved.
Summary
Review of glomerular diseases and ARF Pathology Clinical presentation Diagnosis and treatment Research opportunities
Taper prednisone
14
Questions ?????
15