Case 1: Diagnosis & Conclusions

Case Published: June 2018

Case 1 Index

Diagnosis: Post-Infectious Glomerulonephritis (PIGN)

Case Summary:

Not a straightforward case! Let’s break it down, starting from the HPI. We start off with a woman with a history of mild chronic kidney disease (CKD), diabetes, and hypertension with a recent admission for cellulitis, now taking an antibiotic. We see that her creatinine was 1.5 mg/dL per week ago – thus, we are dealing with an acute process (and thus less likely just progression of her CKD or diabetic nephropathy).

The physical exam tells us she has evidence of volume overload (peripheral edema, pulmonary edema) and that the cellulitis is improving. A differential at this point would include rapidly progressive glomerulonephritis (RPGN, given the rapid rise in creatinine) and acute interstitial nephritis (AIN, maybe from the new antibiotic). Less likely diagnoses on the differential would be progression of diabetic nephropathy and hypertensive nephropathy/hypertensive emergency.

Classification of RPGN (click below!)
Anti-glomerular basement membrane disease
Also known as Goodpasture’s disease, typically affects the small vessels of the kidney and lung and can be diagnosed by biopsy and an elevated anti-GBM antibody titer.
Immune-complex mediated
Can be secondary to wide variety of immune-complex mediated disease including systemic lupus erythematosus (SLE), hepatitis C virus, IgA nephropathy, post-infectious glomeruonephritis, etc.
Usually ANCA associated, and named because of the absence of immune complex deposition (absence of deposits on electron microscopy and negative immunofluorence)

Let’s take a look at the laboratory data. The urinalysis shows us red blood cells, red blood cell casts, and sub-nephrotic range proteinuria – suggestive of glomerular injury and a nephritic syndrome. The absence of white blood cells (pyuria) makes acute interstitial nephritis less likely. Negative anti-GBM antibody and ANCA titers suggest that we are looking for an immune-complex mediated disease, and the low complement levels or hypocomplementemia (C3 is markedly decreased compared to C4, suggesting activation of the classical complement pathway) further support this. The kidney ultrasound shows a normal kidney with normal size and echogenicity, and no hydronephrosis.

Need a way to remember the low-complement diseases? Try this mnemonic (click below!):
*Cryoglobulinemia, C3 glomerulopathy
*Heavy chain deposition disease
*Atheroembolic disease
*Membranoproliferative glomerulonephritis (MPGN)
*Post-infectious + infection-associated glomerulonephritis
*Systemic lupus erythematosus (SLE)

If our differential is right, histology on the H&E should show us a proliferative glomerulonephritis – which it does! We see obliteration of the capillary loops, and endothelial cell proliferation. Neutrophils are also visible within the capillary loops.

Labled PIGN PAS.png

The clincher for this diagnosis is the EM and IF – we see the classic subepithelial hump-like deposits (remember, subepithelial means in the basement membrane and closer to the podocyte) and granular IF staining of C3  (“starry sky” or garland-type deposits) and IgG.

Labled PIGN EMLabeled PIGN IF

The clinical presentation of PIGN is diverse, but classically patients present within a few weeks of active infection. Though this disease typically affects children, adults are also at risk. Don’t let the negative ASO titer in this case fool you – PIGN can present after non-streptococcal infections!

The treatment? Supportive care. There may be a role for corticosteroids, cytotoxic agents, immunosuppressants, or anticoagulants – but no randomized control trials have been done to test these medications.

For a deeper dive, take a look at the references below:

  1. Kanjanabuch T, Kittikowit W, Eiam-Ong S: An update on acute postinfectious glomerulonephritis worldwide. Nat. Rev. Nephrol. 5: 259–269, 2009
  2. Kambham N: Postinfectious glomerulonephritis. Adv. Anat. Pathol. 19: 338–347, 2012
  3. Nasr SH, Fidler ME, Valeri AM, Cornell LD, Sethi S, Zoller A, Stokes MB, Markowitz GS, D’Agati VD: Postinfectious Glomerulonephritis in the Elderly. J. Am. Soc. Nephrol. 22: 187–195, 2011

Case 1 Index
Case 1 Introduction
Case 1 Physical Exam
Case 1 Diagnostic Testing
Case 1 Pathology
Case 1 Additional Pathology