Unusual cause of Renal failurePresentation Transcript
Physicians Meet – M2Case Presentation Prof. Dr. S. Sundar’s Unit Presented by Dr. DeepuSebin
Ponnammal , 55 yr old female House wife First admitted with complaints of Abdominal distention – 1 month Swelling of legs – 1 month
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
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
General Examination PR – 80/min BP - 110/70 mmHg JVP – elevated No pallor/cyaosis/clubbing/lymphadenopathy BPPE + No Signs of liver cell failure
Systems P/A Distented Free Fluid + No organomegaly BS + Chest Clear AEBE CVS S1 S2 normal CNS NFND PEARL
Bilirubin – 1.0 mg/d SGOT- 90 u/l SGPT – 53 u/l ALP – 145 u/l Total Protein – 5.9g.dl Albumin –2.9 g/dl Globulin – 1.8 g/dl INR 1.2
Urine Rountine Albumin - + Sugar – Nil Depostis –1-3 pus cells 10-12 RBCs
DCLD – Portal Hypertension , HBV related AKI - ? Cause to r/o HRS Non oliguric
Urine Sodium – 22meq (<20 pre renal & >40 ATN) UNa x PCr FENa, percent = — — — — — —x 100 — PNa x UCr FeNa – 0.8 (<1 prerenal , > 2 ATN )
Plasma Urea / Creatine Ratio – 37.2 (>30 prerenal) Urine to plasma creatine ratio - 24 (<20 ATN , >40 pre renal ) Urine Creatininre – 43mg/dl
Diuretics including Spironolactone stopped Syrup Laculosetemporarly withdrawn Antibiotics ( Cefotaxime, Metrogyl ) initiated Maintained adequate fluid intake orally Hypovolemia ruled out No hematemesis or malena No loose stools
24 hour urine protein – 2gm Volume 1500 ml
In view of the Elevated renal parameters Which is static Not resolving with conservative management Proteinuria Proceeded with Renal Biopsy after Nephrology Review
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.
Full House pattern IgM, IgG, IgA, C3c, and C1q Possibility of Lupus Nephritis, vasculitis and other connective tissue disorders with DPGN – full house pattern.
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)
In Hepatits B virus related Glomerular pathology we expect membranous glomerulonephritis, or membranoproliferativeglomerulonephritis Here we have Active Hepatitis HbeAgpostivity High Viral Load Absence of other infection, Connetive tissue disorders clinically and radiologicaly. This is a case of HBV related DPGN
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 malignant hypertension. Razzak IA, Bauer W, Itzel W. Full-house nephropathy in a patient with negative serology for lupus Esra Baskin, PınarIsikAgras, NurcanMenekşe, Handan Ozdemir and NurcanCengiz
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.
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
Focal Nephritic Diffuse Nephritic Nephrotic
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.
Focal Nephritic - DDs Active urine sediment without renal insufficiency or nephrotic syndrome Less than 15 years - Mild postinfectiousglomerulonephritis, IgA nephropathy, thin basement membrane disease, hereditary nephritis, Henoch-Schönleinpurpura, 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
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.
Diffuse Nephritic - DDs Active urine sediment with renal insufficiency and variable proteinuria, which can include nephrotic syndrome Less than 15 years - Postinfectiousglomerulonephritis, membranoproliferativeglomerulonephritis 15 to 40 years - Postinfectiousglomerulonephritis, lupus, rapidly progressive glomerulonephritis, fibrillaryglomerulonephritis, membranoproliferativeglomerulonephritis Greater than 40 years - Rapidly progressive glomerulonephritis, vasculitis (including mixed cryoglobulinemia), fibrillaryglomerulonephritis, diffuse proliferaive nephritis, postinfectiousglomerulonephritis
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 moremarked glomerular leakthan those with heavy proteinuria alone. Differntial Diagnosis – all the range of nephrotic disorders Patients with Nephroticproteinuria but no hypoalbuminemia or edema – Suspect some form of secondary focal glomerulosclerosis(as with reflux nephropathy)
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 !
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 Crescenticglomerulonephritissuperimposed upon membranous nephropathy. Nephrotic syndrome secondary to monoclonal immunoglobulin deposition disease may also develop myeloma cast nephropathy and acute renal failure.
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, postinfectiousglomerulonephritis (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, postinfectiousglomerulonephritis (later stage)
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. Nephroticproteinuria 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
Renal Failure in Cirrhosis Hepatorenal Syndrome Psuedohepaorenal Syndrome
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
Type I hepatorenalsyndrome 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 hepatorenalsyndrome 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.
Liver and Kidney
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.
Hepatits B virus and Kidney Infection with hepatitis B virus (HBV) may be directly associated with a variety of renal diseases, including polyarteritisnodosa, membranous glomerulonephritis, and membranoproliferativeglomerulonephritis
Treatement Antiviral therapy targeted against HBV. Steroids and Immunosuppressants and/or Plasma exchange in cases with RPGN features or vasculitis. Conservative management in rest.
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 polyarteritisnodosa. Arthritis Rheum 2004; 51:482. Wen, YK, Chen, ML. Remission of hepatitis B virus-associated membranoproliferativeglomerulonephritis in a cirrhotic patient after lamivudine therapy. ClinNephrol 2006; 65:211.
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
Membranoproliferativeglomerulonephritis The deposition of circulating antigen-antibody complexes in the mesangium and subendothelial space characterizes the membranoproliferativeglomerulonephritis 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.
Polyarteritisnodosa — 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
Diffuse Proliferative Glomerulonephritis A distinct form of glomerulonephritis common to Autoimmune Disorder (eg SLE) Vasulitis Syndrome ( egWegenersGranulomatosis) Infectious Process More than 50 % of glomeruli shows an increase in mesangial, epithelial and enothelialproliferaive and inflammatory cells If less than 50% focal proliferative
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
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