Nephrology Case Nephrology Case PresentationPresentation

Douglas Stahura D.O.

Grandview Hospital

November 20, 2001

Case PresentationCase Presentation

24 y/o AAF referred by PCP c/o fatigue, periorbital edema, lower extremity edema, hematuria, proteinuria

Pt relates a 5 year history of intermittent gross hematuria usually associated with “colds”

Over past four months has noticed increasing fatigue, swelling “around my eyes, especially in the morning” and swelling in the ankles and legs

Case PresentationCase Presentation

PMH – one pregnancy, uncomplicated PSH – none Allergy – none Meds – Lasix 40 mg QD Social – married, nursing student,

nonsmoker, EtOH socially, caffeine-2 cpd Family – Father deceased age 50 MVA,

Mother DM2 age 56

Case PresentationCase PresentationROS

– Fatigue, Weight gain 10#, No energy, poor appetite,

– Swelling in feet/ankles, worse at end of the day, legs “feel heavy”

– Denies CP/PALP/DOE, Cough/Sputum/SOB

– Denies N/V/D, +/-Constipation– No recent UTI, hematuria

Case PresentationCase Presentation

Exam: BP 135/85, T-98.6, P-80, R-14Wt-146, Ht-5’3”NAD, pleasant, cooperativeCV,RESP,GI,MS, LYMPH – WNLSKIN – warm/dry, 3+ pitting up to knees

B/L, no rash/purpura,

Case PresentationCase Presentation

Lab data:– Na-133, K-4.1, Cl-103, HCO3-25– BUN-8, Cr-0.8– CBC normal– AST-18, ALT-22, ALP-80, ALB-0.6– UA SG-1.020, pH-5, BLO-2+, PRO-4+,

GLU-neg, Ketones-Neg– CXR-normal

Differential DiagnosisDifferential Diagnosis

Hematuria, grossProteinuriaHypoalbuminuriaNephrotic SyndromeNephritic Syndrome

Clinical InvestigationClinical Investigation

Imaging: Renal UltrasoundLab:

– ANA, dsDNA– ASO titer, ANCA, anti-GBM Ab– Serum/Urine Electropheresis– HBV, HCV, HIV, C3, C4, CH50– 24 hour Urine: Protein, Creatinine

Renal Biopsy

Clinical InvestigationClinical Investigation

24 hour urine– 18 grams protein/24 hours– Creatinine Clearance 120 ml/min

00:00

IgA NephropathyIgA Nephropathy

Mesangial proliferative glomerulonephritis characterized by diffuse mesangial deposition of IgA

Described by Berger in Paris 1968 Common clinical presentation is gross

hematuria provoked by mucosal infection Diagnosis is made by Immunoflorescence

IgA NephropathyIgA NephropathyPathogenesisPathogenesis

IgA preferentially deposits in glomerulusAbnormality of host IgA immune system

– No consistent evidence for a specific antigen

Bacterial, viral, food

– Possibly autoimmune against mesangium– Antigen-independent mechanism – IgA

glycosylation

IgA NephropathyIgA NephropathyPathogenesisPathogenesis

IgA most abundant Ig in the body and provides mucosal defence

Two subclasses: IgA1, IgA2Mucosal Ag challenge provokes pIgA by

plasma cells in MALTBone marrow derived mIgA1

IgA NephropathyIgA NephropathyPathogenesisPathogenesis

In IgA nephropathy– pIgA1 is deposited in mesangium– pIgA1 is downregulated in mucosa and

upregulated in the marrow– Tonsillar pIgA1 is increased

Mesangial proliferation is a result of cytokines and growth factors (PDGF, TGF-beta)

IgA NephropathyIgA NephropathyClinical PresentationClinical Presentation

Macroscopic Hematuria in 2nd & 3rd decades of life (40-50%)

“Synpharingitic” hematuria Microscopic hematuria +- proteinuria Nephrotic Syndrome w/ hematuria(5%) Acute Renal Failure (rare)

– Cresentic or tubular occlusion by hematuria

Chronic Renal Failure w/HTN

IgA NephropathyIgA NephropathyClinical AssociationsClinical Associations

IgA NephropathyIgA NephropathyPrognosisPrognosis

Clinical– POOR

Increasing Age Duration of symptoms Severity of proteinuria Hypertension Renal impairment

– NO IMPACT Gender Serum IgA level

Histopathologic– POOR

Glomerular sclerosis Tubule atrophy Interstitial fibrosis Vascular wall

thickening Capillary loop wall IgA

deposits

IgA NephropathyIgA NephropathyTherapyTherapy

Reduce IgA production Tonsillectomy Gluten free diet – neither reduce incidence of

renal failure

Altering Immune and Inflammation In cresentic IgAN – plasmapheresis, steroids,

and cyclophosphamide – poor long term results Steroids – alternate day regimen x 2 years Cyclophosphamide only – no good data

IgA NephropathyIgA NephropathyTherapyTherapy

Altering Immune and Inflammation Dipyridimole and warfarin – no benefit Cyclosporine – hemodynamic effect only

Slowly Progressive Hypertension – Use of ACE-Inhibitor to target

125/75 will reduce proteinuria Fish Oil – 4-8 grams/day provided renal

protection from progressive disease, but did not lower proteinuria

My PatientMy Patient

Daily Prednisone, then to alternate day therapy – Failed, no decrement of renal function, but no improvement of proteinuria

Fish Oil – unable to comply and quit therapy after 3-4 months

Cytoxan/Methyprednisolone monthly IV pulses x 6 (Lupus Nephritis regimen)

Albumin =4.1 clinical Nephrotic syndrome resolved

ReferencesReferences

Comprehensive Clinical Nephrology, RJ Johnson/J Feehally, Harcourt, 2000

The Kidney, Brenner and Rector, 6th Ed, Saunders, 2000

The long term Outcome of Patients with IgA Nephropathy Treated with Fish Oil in a Controlled Trial, Donadio et al., JASN:10;1772-1777, 1999