Nephrology‎ > ‎

Proteinuria / Nephrotic and Nephritic Syndrome

    • 3 Principles of evaluation of Proteinuria
      • Think of the source (if clinically needed Urine Protein Electrophoresis can be done)
        • Kidney
          • Glomerulus: as Nephrotic or Nephritic Syndrome
          • Tubules: Other features of Tubulointerstitial Nephritis
        • Post-Renal
          • Ureter, Bladder: as in UTI
      • Dipstick Urine
        • Look for specific gravity
          • Dilute urine with 1+ protein may be more clinically relevant, than concentrated urine with 3+; Do not just rely on protein
          • Light chain will be negative in Dipstick
      • Protein Assessment
        • Urine Protein / Creatinine Ratio
        • 24 hr Urine Protein assessment 
    • Interpreting and investigating proteinuria BMJ 2013 
    • Case 5-2010 (Glomerulonephritis in HCV, HIV patient) 

    • Primary
    • Secondary
      • DM
      • Amylodiosis
      • MGRS or MM
Case 35-2015: A 72-Year-Old Woman with Proteinuria and a Kidney Mass
    • RPGN:  
      • RPGN Classification Case 3-2014
        • a) Anti - GBM 
        • b) ANCA Associated Vasculitis 
          • GPA 
          • Microscopic Polyangitis (formerly Wegner's granulomatosis)
          • Eosinophilic GPA (formerly Churg-Strauss Syndrome)
          • Pauci-Immune Crescentric Polyangitis
        • c) Immune complex disease 
          • Low Complement Immune Complex Disease vs 
          • Normal Complement Immune Complex Diseases (direct Ig deposition)
            • Ig A Nephropathy
            • HSP
            • Fibrillary GN
            • Immunotactoid GN
      • For more also see Clinical Immunology and Nephrology
Appreciate 3 major disease process causing RPGN (Anti-GBM, ANCA, Immune-Complex mediated disease)

Appreciate 4 main causes of MPGN (Infections, Monoclonal Gammopathies, Collagen Vascular Disease, Genetic/Acquired Diseases)

In Table 2 above, appreciate that MPGN has low complement level. 
In the etiological cause of MPGN (below), appreciate how that low complement is either due to Immune Complex Mediated Disease (Classic Pathway activation) or Compliment mediated disease (Dysregulation of alternate pathway itself)
  • MPGN — A New Look at an Old Entity NEJM 2012
    • Old way to look at MPGN
      • Primary:
        • MPGN I (Subendothelial Deposits)
        • MPGN II (Dense deposits in GBM)
        • MPGN III (Subendothelial + Subepithelial Deposits)
      • Secondary
        • HCV (is the most common cause)
    • New way to look at MPGN
      • Immune-Complex Mediated (Classic pathway activation)
        • Autoimmune Ds
        • Paraproteinemia due to MGRS
        • HCV (main cause of MPGN) and other infections
        • Lab evaluation: Low C3 and Low C4
      • Complement Mediated (dysregulation of alternate complement pathway)
        • Dense Deposit Disease
        • C3GN
        • Lab evaluation: Low C3 and Normal C4 (normal C4 does not rule out alternate pathway dysfunction)


Case Description
  • 30 yr old F is seen for anuria of 1 week, and weakness of 2 weeks. Following were the labs. CMP, CBC, and UA is as below. 

Does have proteinuria. Given this finding what is the DDx and how should this be worked up? Complement level was normal. NO skin rash, or joint pain. 

Syndromic Diagnosis. RPGN with Nephrotic Range Proteinuria 


  • collapsing glomerulopathy, a variant of focal segmental glomerulosclerosis, typically present with a rapid progression of renal failure and heavy proteinuria.
  • Minimal-change disease associated with acute tubular injury is another such condition; tubular injury is thought to be explained by ischemic injury or severe interstitial edema 
  • Ig A nephropathy is a DDx. 
  • Other considerations
    • Anti-GBM , ANCA vasculitis, Fibrillary GN, Immunotactoid GN
Next step in Management:
  • Renal Biopsy
  • Anti-GBM
  • ANCA

Case Discussion 2

55 yr of AAM is seen for SOB and headache. No PMHx, and NO prior medication.  Following is the finding on presentation. 


PTH is elevated. PO4 3 - is elevated. Calcium is low. ABG shows primary respiratory alkalosis with appropriate compensation.

What is the syndrome. 

Nephrotic Syndrome 

What is the cause? Nephrotic syndrome that can cause elevation of Cr to this extent is either due to 
  • MCD with ATN 
  • FSGS , collapsing variant 
  • MPGN 
  • Secondary cause: DM, Amyolidiosis, and MM
SPEP, S - IFA, FLC, A1C are normal. LFT and Cardiac ECHO seems normal as well. Complement is normal. 

Hence, remaining DDx are 
  • MCD with ATN 
  • FSGS , collapsing variant 
Next step in Managemnt. 

Renal Biopsy. 

  • Initial Biopsy results shows Membranous Nephropathy.