2.  History:  Gross hematuria  Frothy urine  HTN  Recent/chronic illness (URI, Hep C, HIV, etc.)  History of rheum disease or + ROS  History of Cancer or + ROS  Family history  Increased edema

3.  Active urine sediment:  Granular/muddy brown casts  Sterile pyuria vs. WBC casts  Dysmorphic RBCs vs. RBC casts  Proteinuria  Nephrotic range proteinuria  Non-nephrotic range proteinuria  Paraproteinemia  Progressive unexplained decline in GFR

12.  Nephrotic syndrome:  NRP: > 3.5 gm  Low Albumin  High cholesterol  Lipiduria  Edema  More bland urine sediment  Decreased change of HTN  Pro-thrombotic state

13.  MCD  Membranous GN: primary and secondary  FSGS: primary and secondary  IGM nephropathy  DM  Fibrillary GN  C1q nephropathy  Amyloidosis  IgA nephropathy  PSGN, Lupus etc

14.  Nephritic  HTN  Active urine sediment (Dysmorphic RBC/RBC cast)  NNRP or NRP  Edema with volume overload  Oliguric  Reduced GFR

15.  Lupus  IgA nephropathy  PSGN  Vasculitis (Wegener’s, MPA, CS)  Anti-GBM disease  MPGN and Cryoglobulinemia  Malignant HTN  TTP/HUS  Embolic/immune complex deposition disease

16.  Nephrotic Syndrome  As previous  Acute Glomerulonephritis  As previous  Chronic Glomerulonephritis  Insidious/smoldering/slow progressive GN

17.  Rapidly progressive glomerulonephritis  Focal proliferative/necrotizing/Crescents  Rapid decline in renal function (days/weeks)  Vasculitis vs. Anti-GBM dz vs. TMA/TTP vs. IgA nephropathy vs. DPLN vs. PSGN vs. MPGN  Asymptomatic Urinary Abnormalities  Recurrent/persistent non-GU hematuria  TBMD; Alport’s syndrome, IgA  Isolated NNR proteinuria or sterile pyuria  Same differential of NRP or TI dz  Only one finding with no HTN, GFR decline abnormal exam findings

18.  Each disease not limited to one classification  IgA can present with all five  Lupus can present with all five  Disease continuum  AUA to NRP to Acute GN to RPGN (Lupus)  The neurology game of “guess the lesion” while awaiting renal biopsy (our MRI)  Biopsy gold standard, but:  Sample variation: may miss FSGS; Lupus IV/V  Each histopathology diagnosis likely represents multiple pathophysiology mechanisms

19.  ‘Permeability factor’ (evident post transplant)  Genetic (nephrin, podocin, alpha-actin IV)  ESRD common endpoint (hyperfiltration)  Viral infection (Parvovirus, HIV)  Elevated GH levels  Obesity  Reflux nephropathy  Drugs (palmidronate, heroin)

20.  Membranous GN  mesangial involvement suggests secondary cause:  CA screening  ANA; //DNA  Hepatitis panel  FSGS  HIV  Genetic testing  MPGN  Hepatitis panel  Cryoglobulins  C3/C4

21.  Lupus Nephritis  ANA  // DNA  C3/C4/C50  Vasculitis  P-ANCA; C-ANCA  CRP  Anti-GBM disease  Anti-GBM antibody  Acute interstitial nephritis  Serum/urine eosinophils

22.  TMA/TTP  Platelets  Hgb  Haptoglobin, LDH, indirect bilirubin  Peripheral smear  PSGN  ASO  Anti-DNAase  Cryoglobulinemia  Serum cryoglobulins

23.  Paraproteinemia  SPEP, UPEP, Kappa/Lambda light chain ratio  IgA nephropathy  IgA levels NOT diagnostic  Galactose deficient IgA1 associated with disease  IgM nephropathy  IgM levels NOT diagnostic  IgM to IgG ratio could be diagnostic  Minimal Change Disease  none  Fibrillary GN  none

24.  Lupus Nephritis  MPGN  PSGN  Cryoglobulinemia  Embolic/Immune Complex deposition disease

25.  Light Microscopy  Numerous stains: Silver stain GBM/matrix  Hypercellular (proliferative) mesangial/endothelial  Hypercellular (Exudative): Inflammatory leukocytes  Glomerular necrosis : RPGN  Crescents: Collection of inflammatory cells in Bowman’s space  Capillary loop collapse; attachment to Bowman’s  Thickening/division of capillary loops  Tublules: Cells; cell inclusions, lumen contents  Interstitium: Edema, infiltration, fibrosis

26.  Interstitial Edema  Interstitial inflammatory infiltrate  Glomerular hypercellularity  Glomerular Necrosis  Increased mesangial matrix  Congested tubules  Cellular crescents

27.  Interstitial Fibrosis  Tubular Atrophy  Glomerular sclerosis (obsolescence)  Dilated tubules  Results in broad waxy casts on urine microscopy

42.  Immunofluorescence  Evaluation for immune deposits  Detect IgA, IgM, IgG, C3, C4, and C1q  Also Fibrin (Crescents; capillaries in thrombotic dz)  Linear (continuous) or granular (discontinuous)  Anti-GBM: Linear GBM deposits  Membranous GN: Granular GBM deposits  Capillary walls or mesangium  Vasculitis has a ‘pauci-immune’ IF  Lupus has a ‘full house’ IF

47.  Electron Microscopy  Anatomy of GBM (Alport’s, TBMD, MPGN II)  Localization of deposits:  Subepithelial (nephrotic)  Subendothelial (nephritic)  Mesangial (nephritic); secondary membranous  Foot process fusion (nephrotic)  Special deposits (Fibrillary, amyloidosis, LCDD)

57.  Acute therapy (RPGN)  Pulse steroids: ALL  Cytoxan: Lupus; vasculitis; anti-GBM disease, IgA  Plasmapheresis: TTP, Anti-GBM; Vaculitis  Consolidation therapy  MMF (Lupus)  Azothiaprine (vasculitis, lupus)  Acute/Chronic GN  PO steroids  Cyclosporin/tacrolimus  MMF  Rituximab; IVIG; Sirolimus

59.  64 y/o African American female with a history of “arthritis” presents for evaluation of progressive lower extremity edema of two weeks duration. She has no history of CKD, HTN, or DM. Her cancer screening is up to date (all negative/normal). She denies changes in her urination, SOB, fatigue, malaise, loss of appetite, fever, chills or night sweats. She has no personal or family history of renal disease. Her medications include a multivitamin and celecoxib. Her vitals are normalis totalis. Her exam was significant for lower extremity pitting edema to her waist bilaterally. Her labs reveal a serum creatinine of 2.1 mg/dL (up from 0.7 one month ago at her yearly PCM appointment). 24-hour urine protein was 5.6gm. Urine sediment revealed 10-20 WBCs with 3-4 WBC casts.

61.  Additional questions?  Differential Diagnosis?  Additional diagnostic evaluation?  Kidney Biopsy?  Therapeutic intervention?

62.  19 year old active duty male with no past medical history presents with the chief complaint “I was peeing blood doc. I mean straight up tomato soup.” Further questioning reveals that he had a sore throat 1 week ago. He first noted gross hematuria 2-3 days later which has gotten progressively better over the past few days and now it “looks normal.” He also reports 3/10 bilateral flank pain and some overall fatigue/malaise. He denies recent trauma, dysuria, urgency, frequency, nausea, vomiting, lower abdominal discomfort, fever/chills/night sweats, rashes, or skin lesions. He is not sexually active. He denies past gross hematuria but did have one episode of “dusky” urine a few years back. He denies past kidney problems but thinks that his mom “has always had a little blood in her urine but not so you can see it.” He takes no medications and denies taking dietary supplements. Vitals normalis totalis. There were no significant findings on exam. Labs reveal a serum Creatinine of 0.7mg/dL with no historical comparison. UA is negative for protein. Urine sediment reveals:

66.  Differential Diagnosis?  Additional diagnostic evaluations?  Kidney Biopsy?  Therapeutic intervention?  Would a Cr of 2.0 and 4gm of proteinuria change the differential diagnosis, diagnostic work up, and/or therapy?

70.  A 92 y/o Caucasian female presents with progressive fatigue, malaise, loss of appetite, and weight loss of 3 months duration. She also reports a chronic URI of 3 months duration unresponsive to 3 separate courses of different antibiotics. She denies hemoptysis, fever, chills, night sweats, nausea, vomiting, abdominal pain, early satiety, bloody/black BMs, HA, focal motor/sensory deficits, bony pain, change in urination. Her cancer screening is up to date (all normal/negative). She takes only a daily MVI and weakly Fosamax. She denies a personal or family history of kidney disease. She was mildly hypertensive. There were no significant findings on exam. Her labs reveal a serum Creatinine of 2.5 mg/dL up from a baseline of 0.9mg/dL 3 months ago. Her urine sediment revealed 30-50 RBCs phf (<10% dysmorphic) with occasional RBC cast. A 24-hour urine protein was 1.3gm. Her serum albumin was 2.2 and Hgb was 9.7. 

72. Differential Diagnosis? Additional diagnostic evaluations? Kidney Biopsy? Therapeutic intervention?

79.  A 55 y/o Caucasian male saw his PCM 2 weeks prior for progressive LE swelling of 2 weeks duration. He had no complaints and his ROS was negative. At the time his creatinine was noted to be at baseline 0.9mg/dL. His 24-hour urine protein was 13gm. His UA was negative for blood. LE dopler US was negative for clot. He presents for his nephrology consult 2 weeks later complaining of right sided loin/flank pain of 2 days duration with worsening LE edema, decreased appetite, early satiety, and feeling bloated. Exam reveals anasarca with no flank tenderness. Labs reveal a Cr of 1.4 mg/dL and an albumin of 1.5. His urine sediment reveals 20-30 non-dysmorphic RBCs phf.

80.  Differential Diagnosis?  Additional diagnostic evaluations?  Kidney Biopsy?  Therapeutic intervention?

86.  A 22 y/o African American female admitted for bilateral pleural effusions and desaturation with ambulation after presenting with complaints of DOE during her runs. ROS is significant for increased fatigue prior to the DOE, arthralgias and some hair loss. Decreased BS at the bases with no m/r/g or distant heart sounds appreciated. Asymetry left lower extremity swelling of 1 week duration. Her labs reveal a creatinine of 1.3. Her spot urine protein/cr ratio demonstrates 1.5gm of protein. Hgb 9.7. Her urine sediment has 10-20 RBCs phf (20% dysmorphic) with no WBCs and no casts.

87.  Additional diagnostic evaluations?  Kidney Biopsy?  Therapeutic intervention?