Case 355-year man presenting with nephrotic syndrome and RPRF

Dr. Vinita AgrawalAdditional Professor

Department of PathologySGPGIMS, Lucknow

Clinical presentation

• 55 year gentleman • Not a known diabetic/ hypertensive• Edema- 1month• Decreased urine output- 2weeks• Fever with chills- 2weeks• Breathlessness-2weeks• Anorexia, nausea, recurrent vomiting- 2weeks

Clinical presentation

• No history of–Hematuria– systemic symptoms: cough, expectoration,

joint pains, rashes, sore throat

On examination

• PR-110/min• BP- 180/90 mm Hg• Pallor+, edema+• Chest- bilateral crepitations• No organomegaly

InvestigationsHematological

Parameter Value

Hb 8.8gm/dL

TLC 9300/dL

DLC N62L28E06M04

Platelet 1,20,000/dL

Reticulocyte 1.1%

GBP Normocytic normochromic

Biochemical

Parameter Value Normal

S. Creatinine 7.0 0.5-1.2mg/dl

S. Protein 6.9 6-8.4 g/dl

S. Albumin 3.4 3.5-5.5g/dl

InvestigationsSerology

Parameter Value NormalS. C3 68.8 60-120

mg/dlS. C4 17.6 15-25

mg/dl

Urine examinationParameter ValueOutput 1800pH 5Protein 4+RBC’s 15-20/hpfWBC’s 12-15/hpfCulture Positive

(E.faecalis)

Clinical diagnosis• 55 year-male patient with nephrotic range

proteinuria – Recent onset– Renal failure– Active sediments

RPRF with nephrotic range proteinuria? Crescentic GN

Renal histology

Salient histological features

Enlarged glomeruliDiffuse endocapillary proliferationNeutrophilic exudationWidespread splitting of GBMCapillary BM thickening (wire loop-like)Hyaline thrombiAcute tubular necrosis

Histological diagnosis and differential diagnosis

Proliferative Glomerulonephritis(MPGN)

• MPGN type I • C3 glomerulopathy • Cryoglobulinemia• Lupus Nephritis• Secondary GN- HCV or HBV related?

IgG (3+) IgA (4+)

C3 (4+)

IgM, C1q negative K, λ equal intensity

EM findings

• Focal foot process effacement• Extensive electron dense deposits: sub-

endothelial and in capillary lumens• Glomerular basement membrane duplication

Further work-up

InvestigationsSerology

Parameter Value NormalANA negativeAnti-GBM ab. negative <15au/mlANCA negative MPO <3au/ml

PR3 <3au/ml S. Cryoglobulins negativeHIV negativeHBsAg negativeHCV negative

Final Diagnosis• Cryoglobulinemia

x S. Cryoglobulins negativex No hyper-gammaglobulinemia

• Lupus Nephritisx No systemic manifestationsx ANA negativex Full-house on IF absent

• Secondary causes- HCV or HBV x Serology negative

• C3 glomerulopathy and dense deposit diseasex Presence of IG’s on IFx S. C4 low (marginally)x No dense deposits on ultrastructure

• MPGN type I

Final Diagnosis

• IgA Nephropathy with MPGN-like pattern (M1E1S0T0)/HAAS Class IV ? Features

Extensive sub-endothelial depositsHyaline thrombi and wire loop-like lesions

• MPGN type I (IgA-dominant)

IgA Nephropathy with MPGN-like pattern

• Rare; few case reports• Usually reported in children* • IgA-dominant post-infectious GN may have a

MPGN-like pattern and hyaline thrombi ǂ

* Iitaka, K. IgA-associated GN with MPGN-like pattern in 2 children. Clin.Exp. Nephrol. 2003; 7:284-9.* Akira K et al. Infantile IgAN showing features of MPGN. Tohoku J Exp. Med. 2012;228:253-58.

ǂWorawichawong S et al. IgA-dominant postinfectious GN. Hum. Pathol. 2011; 42: 279-84 Satoskar A et al. Staph. infection-associated GN mimicking IgAN . Clin J Am Soc Nephrol. 2013;1: 1179.

• No description of MPGN-like pattern • Peripheral capillary deposits (23%) had no

prognostic significance

Summary

• Diagnostic dilemma- IgAN with MPGN- like pattern/ MPGN (IgA-dominant)

• Limited description in literature• No association with the common secondary

causes

Follow-up

Intensive treatment- Steroids (3 months)

RemissionMaintenance on Azoran + ACE receptor blockers• Recent visits (Feb. and August 2013)• S. creatinine- 1.2mg%, no proteinuria or active

urinary sediments