1. Physicians Meet – M2
Case Presentation
Prof. Dr. S. Sundar’s Unit
Presented by Dr. Deepu Sebin
2. Ponnammal , 55 yr old female
House wife
First admitted with complaints of
Abdominal distention – 1 month
Swelling of legs – 1 month
3. Gradually progressing abdominal distention over one
month.
Breathlessness with moderate exertion.
No orthopnea / PND.
Sweling of both legs for 1 month
Swelling of legs mainly in the evenings.
No history of nausea or vomiting.
No history of malena/hematemesis.
No history of decreased urine output.
No history arthralgia/ oral ulcers
4. Past History
No history DM/SHT/PTB/ Jaundice/ CAD/ Surgeries/Drug
Intake
No history of blood transfusions
Personal History
Post Menopausal status
Mixed Diet
Family History
Nil Specific
5. General Examination
PR – 80/min
BP - 110/70 mmHg
JVP – elevated
No pallor/cyaosis/clubbing/lymphadenopathy
BPPE +
No Signs of liver cell failure
6. Systems
P/A
Distented
Free Fluid +
No organomegaly
BS +
Chest
Clear
AEBE
CVS
S1 S2 normal
CNS
NFND
PEARL
19. Plasma Urea / Creatine Ratio – 37.2
(>30 prerenal)
Urine to plasma creatine ratio - 24
(<20 ATN , >40 pre renal )
Urine Creatininre – 43mg/dl
20. Diuretics including Spironolactone stopped
Syrup Laculose temporarly withdrawn
Antibiotics ( Cefotaxime, Metrogyl ) initiated
Maintained adequate fluid intake orally
Hypovolemia ruled out
No hematemesis or malena
No loose stools
21. 1st adm Day 14 Day15 Day 18 Day 20 Day 22 Day 28 Day 29
Blood
Urea
42 67 56 60 49 56 63 59
S.Creati
nine
1.2 1.8 1.7 1.6 1.4 1.8 1.7 1.8
Urine
Albumin
+ Nil ++ ++ +++ +++ ++ +++
24 hour urine protein – 2gm
Volume 1500 ml
22. In view of the
Elevated renal parameters
Which is static
Not resolving with conservative management
Proteinuria
Proceeded with Renal Biopsy after Nephrology Review
23.
24.
25. Sections show renal tissue with eight glomeruli per
sections. These are enlarged and hypercellular with
endothelial and mesangial proliferation with infiltration by
few neutrophils. Focal splitting of capillary wall noted. No
capillary wall thickening is seen. There is no tubular
atropy. Blood vessels appear unremarkable
Immunofluorescence stains show peripheral granular
deposits in IgM, IgG, IgA, C3c, and C1q
Impression : Renal Biopsy showing Diffuse
Proliferative Glomerulonephritis and mild
exudation and no significant tubuointerstitial changes.
26. Full House pattern
IgM, IgG, IgA, C3c, and C1q
Possibility of Lupus Nephritis, vasculitis and other
connective tissue disorders with DPGN – full house
pattern.
27. ANA – negative (Repeated)
ds DNA – negative
ASO titer - < 100
p-ANCA and c- ANCA – Negative
C3 – 53.04 (90 – 180mg/dl)
C4 – 13. 78 (10- 40 mg/dl)
29. In Hepatits B virus related Glomerular pathology we
expect
membranous glomerulonephritis, or
membranoproliferative glomerulonephritis
Here we have Active Hepatitis
HbeAg postivity
High Viral Load
Absence of other infection, Connetive tissue disorders
clinically and radiologicaly.
This is a case of HBV related DPGN
30. Final Diagnosis
HBV infection related Diffuse Proliferative
Glomerulonepheritis
HBV related DCLD and PHT
Am J Gastroenterol. 1995 Jun;63(6):476-80.
Hepatitis-B-antigenemia with panarteritis, diffuse proliferative glomerulitis and malig
Razzak IA, Bauer W, Itzel W.
Full-house nephropathy in a patient with negative serology for lupus
Esra Baskin, Pınar Isik Agras, Nurcan Menekşe, Handan Ozdemir and Nurcan Cengiz
31. Treated with
T. Lasix 40mg BD
T. Lamividine 100mg OD
T. Propranalol 20 BD
T. Rantac 50mg BD
Syp. Lactulose 15ml TID
Pulse Methylprednisolone therapy reserved if patient
develops worsening of her renal failure.
32. Simplified Appraoch to Glomerular Disease
Glomerular Disease a diagnosis before biopsy
— Although there are many causes of glomerular
disease, the patient's age and the
characteristics of the urine sediment usually
allow the differential diagnosis to be narrowed prior
to renal biopsy
34. Focal nephritic
Focal nephritic —
Focal glomerulonephritis is associated with inflammatory
lesions in less than one-half of glomeruli on light
microscopy.
The urinalysis reveals
red cells (which often have a dysmorphic appearance)
red cell casts, and
mild proteinuria (usually less than 1.5 g/day).
The findings of more severe disease are usually absent,
including nephrotic range proteinuria, edema, hypertension, and
renal insufficiency. These patients often present with
asymptomatic hematuria and proteinuria discovered on routine
examination.
35. Focal Nephritic - DDs
Active urine sediment without renal insufficiency or
nephrotic syndrome
Less than 15 years - Mild postinfectious
glomerulonephritis, IgA nephropathy, thin basement
membrane disease, hereditary nephritis, Henoch-
Schönlein purpura, mesangial proliferative
glomerulonephritis
15 to 40 years - IgA nephropathy, thin basement
membrane disease, lupus, hereditary nephritis, mesangial
proliferative glomerulonephritis
Greater than 40 years - IgA nephropathy
36. Diffuse Nephritic
Diffuse nephritic —
Diffuse glomerulonephritis, in comparison, affects most or
all of the glomeruli.
Thus, the urinalysis is similar to focal disease, but heavy
proteinuria (which may be in the nephrotic range),
edema, hypertension, and/or renal insufficiency may be
seen.
37. Diffuse Nephritic - DDs
Active urine sediment with renal insufficiency and
variable proteinuria, which can include nephrotic
syndrome
Less than 15 years - Postinfectious glomerulonephritis,
membranoproliferative glomerulonephritis
15 to 40 years - Postinfectious glomerulonephritis,
lupus, rapidly progressive glomerulonephritis, fibrillary
glomerulonephritis, membranoproliferative
glomerulonephritis
Greater than 40 years - Rapidly progressive
glomerulonephritis, vasculitis (including mixed
cryoglobulinemia), fibrillary glomerulonephritis, diffuse
proliferaive nephritis, postinfectious glomerulonephritis
38. Nephrotic —
Heavy proteinuria and lipiduria,
But few cells or casts
Bland proteinuria
Patients who also have edema and hyperlipidemia (the
full-blown nephrotic syndrome) tend to have a more
marked glomerular leak than those with heavy
proteinuria alone.
Differntial Diagnosis – all the range of nephrotic disorders
Patients with Nephrotic proteinuria but no
hypoalbuminemia or edema – Suspect some form of
secondary focal glomerulosclerosis (as with reflux
nephropathy)
39. The relatively bland sediment in the nephrotic
disorders results from the
lack of inflammatory cell infiltration in the glomeruli
absence of immune complex deposition in most of these
disorders
The lack of inflammation also results in the plasma
creatinine concentration being normal or only slightly
elevated at presentation in the nephrotic disorders !
40. Renal Failure + Nephrotic Syndrome
Concurrent acute tubular necrosis, esp in MCD
Tubular injury in collapsing focal
glomerulosclerosis, either idiopathic or associated
with HIV infection. (Collapsing FSG)
Minimal change disease with acute interstitial
nephritis due to NSAIDs
Crescentic glomerulonephritis superimposed
upon membranous nephropathy.
Nephrotic syndrome secondary to monoclonal
immunoglobulin deposition disease may also
develop myeloma cast nephropathy and acute
renal failure.
41. Nephrotic - DDs
Heavy proteinuria, bland sediment although some
hematuria allowed .
Less than 15 years - Minimal change disease, focal
glomerulosclerosis, mesangial proliferative
glomerulonephritis
15 to 40 years - Focal glomerulosclerosis, minimal change
disease, membranous nephropathy (including lupus),
diabetic nephropathy, preeclampsia, postinfectious
glomerulonephritis (later stage)
Greater than 40 years - Focal glomerulosclerosis,
membranous nephropathy, diabetic nephropathy, minimal
change disease, IgA nephropathy, primary amyloidosis or
the related disorder light chain deposition, benign
nephrosclerosis, postinfectious glomerulonephritis (later
42. References
Comprehensive Clinical Nephrology 3rd edition
Rose, BD. Pathophysiology of Renal Disease, 2d ed, McGraw-
Hill, New York, 1987, p. 16
Rose, BD. Clinical characteristics of glomerular disease. In:
Scientific American Medicine, Rubinstein, E, Federman DD
(Eds), Scientific American, New York, 1989, section X (IV):1.
Praga, M, Borstein, B, Andres, A, et al. Nephrotic proteinuria
without hypoalbuminemia:
Clinical characteristics and response to angiotensin-converting
enzyme inhibition. Am J Kidney Dis 1991; 17:330.
Rivera, F, Lopez-Gomez, JM, Perez-Garcia, R, et al.
Clinicopathologic correlations of renal pathology in Spain.
Kidney Int 2004; 66:898. Iseki, K, Miyasato, F, Urhara, H, et al.
Outcome study of renal biopsy patients in Okinawa, Japan.
Kidney Int 2004; 66:914
44. HRS – DIAGNOSIS
Major Criteria — :
Chronic or acute hepatic disease with advanced hepatic failure and portal
hypertension
A plasma creatinine concentration above 1.5 mg/dL that progresses over days to
weeks.
The absence of any other apparent cause for the renal disease, including shock,
ongoing bacterial infection, current or recent treatment with nephrotoxic drugs,
The absence of ultrasonographic evidence of obstruction or parenchymal renal
disease.
Urine red cell excretion of less than 50 cells per high power field (when no urinary
catheter is in place)
Protein excretion less than 500 mg/day.
Lack of improvement in renal function after volume expansion with intravenous
albumin (1 g/kg of body weight per day up to 100 g/day) for at least two days and
withdrawal of diuretics.
Minor Criteria
Urine Volume < 500mg/dl
Urine Sodium < 10 mmol/l
Urine RBC < 50/hpf
Serum Sodium concentration < 130 mmol/l
45. Type I hepatorenal syndrome is the more serious
type; it is defined as at least a 50 percent lowering of
the creatinine clearance to a value below 20 mL/min
in less than a two week period or at least a twofold
increase in serum creatinine to a level greater than
2.5 mg/dL
Type II hepatorenal syndrome is defined as less
severe renal insufficiency than that observed with
type I disease; it is principally characterized by
ascites that is resistant to diuretics.
46. Liver and Kidney
Potential Causes Tubular Involvement Glomerular
involvement
Infections Sepsis, Leptospirosis,
Brucellosis, B, EBV,
Hepatitis B
Hepatitis B and C
Shistosoma Mansoni,
HIV
Drugs and Toxins Nephrotoxic Drugs
Systemic Diseases Sarcoidosis, Sjogren
Syndrome
SLE, vasculitis,
cryoglobulinemian,
Amyloidosis
Circulaory Failure Hypovolemia / shock
Congenital and Genetic PCKD, Nephrolithiasis,
Congenital hepatic
fibrosis
Malignancy Lukemia
Lymphoma
Misc Fatty liver of pregnancy,
Reyes Syndrome
Eclampsia, HELLP
47. References
Comprehensive Clinical Nephrology , 3rd edition-
Feehaly
Brenner and Recotor – The Kindey
Gines, P, Schrier, RW. Renal failure in cirrhosis. N
Engl J Med 2009; 361:1279. Gines, P, Guevara, M,
Arroyo, V, Rodes, J
Hepatorenal syndrome. Lancet 2003; 362:1819.
48. Hepatits B virus and Kidney
Infection with hepatitis B virus (HBV) may be directly
associated with a variety of renal diseases, including
polyarteritis nodosa, membranous
glomerulonephritis, and membranoproliferative
glomerulonephritis
49. Treatement
Antiviral therapy targeted against HBV.
Steroids and Immunosuppressants and/or Plasma
exchange in cases with RPGN features or vasculitis.
Conservative management in rest.
50. Mukhtyar C, Guillevin L, Cid, MC, et al. EULAR
recommendations for the management of primary
small and medium vessel vasculitis. Annals of
Rheumatic Diseases April 2008.
Guillevin, L, Mahr, A, Cohen, P, et al. Short-term
corticosteroids then lamivudine and plasma
exchanges to treat hepatitis B virus-related
polyarteritis nodosa. Arthritis Rheum 2004; 51:482.
Wen, YK, Chen, ML. Remission of hepatitis B virus-
associated membranoproliferative glomerulonephritis
in a cirrhotic patient after lamivudine therapy. Clin
Nephrol 2006; 65:211.
52. Membranous nephropathy
HBV can induce the nephrotic syndrome due to
membranous nephropathy. It has been proposed,
although not proven,
deposition of HBeAg and anti-HBe is responsible for the
formation of pathogenic subepithelial immune deposits
Membranous nephropathy is most common in children
and resolves spontaneously in many cases,
However, resolution is relatively uncommon in adults,
most of whom appear to have progressive disease over
time
53. Membranoproliferative glomerulonephritis
The deposition of circulating antigen-antibody
complexes in the mesangium and subendothelial
space characterizes the membranoproliferative
glomerulonephritis associated with HBV. Both
HBsAg and HBeAg deposition have been implicated in
this
Some patients may have a membranoproliferative
pattern due to mixed cryoglobulinemia; concurrent
infection with hepatitis C to be ruled out.
54. Polyarteritis nodosa — A large vessel vasculitis can
be induced by HBV, in which circulating antigen-
antibody complexes may be deposited in the
vessels.
The vasculitis, which is called secondary PAN and
has the same clinical features as idiopathic PAN that
is not associated with HBV, typically occurs within
four months after the onset of HBV infection
55. Diffuse Proliferative Glomerulonephritis
A distinct form of glomerulonephritis common to
Autoimmune Disorder (eg SLE)
Vasulitis Syndrome ( eg Wegeners Granulomatosis)
Infectious Process
More than 50 % of glomeruli shows an increase in
mesangial, epithelial and enothelial proliferaive and
inflammatory cells
If less than 50% focal proliferative
56. When to suspect DPGN
Suspect DPGN in patients with SLE, infectious disease
processes, a recent streptococcal throat infection, or in
patients with sinopulmonary disease who have recent
onset of the following:
Hypertension
Microscopic or gross hematuria
Nonnephrotic or nephrotic range proteinuria or an
increase in proteinuria from baseline
Serum creatinine of more than 0.4 mg/dL from the
reference range or the baseline
Oligoanuria and symptoms of uremia in severe cases of
RPGN with crescent formation
57. A history of rash; photosensitivity; oral ulcers; arthralgias;
arthritis; serositis; or a renal, neurologic, hematologic, or
immunologic disorder suggests SLE as the primary
disease.
A history of cough, dyspnea, hemoptysis, and renal
disease suggests Goodpasture syndrome, but other
pulmonary-renal syndromes must be ruled out, including
SLE pneumonitis, Wegener granulomatosis,
cryoglobulinemia, renal vein thrombosis with pulmonary
embolism, legionella infection, and congestive heart
failure.
Patients with Wegener granulomatosis present with
sinopulmonary
Atypical Presentations of Ig A Nephropathy
