1. Acute Nephritic Syndrome Dr.Gudigunti Gopi Dept of Nephrology, Rustaq Hospital.

2. 1) Overview 2) Synonymous Conditions 3) Etiology of Ac Nephritic Synd 4) APSGN/APIGN 5) Ac Nephritic Synd Clinical Presentation 6) Workup 7) Management. 3. Acute Nephritic Synd comprises a specific set of renal diseases in which an immunologic mechanism triggers inflammation and proliferation of glomerular tissue that can result in damage to the basement membrane, mesangium, or capillary endothelium. Bright initially described acute glomerulonephritis (GN) in 1927. Acute poststreptococcal glomerulonephritis (APSGN) is the archetype of acute nephritic Synd. Acute nephritic syndrome is the most serious and potentially devastating form of the various renal syndromes. Over view 4. RPGN Rapidly progressive GN (RPGN) describes the clinical situation in which glomerular injury is so acute and severe that renal function deteriorates during days or weeks The histologic counterpart of RPGN is crescentic GN. The proliferative cellular response seen outside the glomerular tuft but within Bowman's space is known as a crescent because of its shape on histologic cross section Unfortunately, not all patients with a nephritic urine sediment and acute kidney injury (AKI) will fit this syndrome. For example, AKI may also occur in milder forms of glomerular disease if it is complicated by accelerated hypertension, renal vein thrombosis, or acute tubular necrosis. This emphasizes the need to obtain histologic confirmation of the clinical diagnosis. 5. Aetiology of Ac Nephritic Synd 6. APSGN/APIGN Etiology The offending organisms are virtually always group A streptococci ( GAS ). Acute poststreptococcal glomerulonephritis (APSGN) follows pyodermatitis with streptococci M types 47, 49, 55, 2, 60 Acute poststreptococcal glomerulonephritis (APSGN) throat infection with streptococci M types 1, 2, 4, 3, 25, 49, and 12. 7. APSGN/APIGN Occurs 10-14 days after URTI NOT SYNPHARYNGITIC CAN OCCUR IN EPIDEMICS Epidemic poststreptococcal glomerulonephritis occurs mainly in developing countries in areas such as Africa, the West Indies, and the Middle East. Incidence is declining in the West due to better antibiotics/hygeine- similar to Ac Rh Heart Disease M : F 2:1 8. Ac Nephritic Syndrome Clinical Presentation History A history suggestive of preceding streptococcal infection may include a preceding infective episode such as pharyngitis, tonsillitis, or pyoderma. This is the sine qua non for the diagnosis of APSGN. In general, the latent period is 1-2 weeks after a throat infection and 3-6 weeks after a skin infection. The onset of signs and symptoms at the same time as pharyngitis (also called synpharyngitic nephritis) is more likely to be immunoglobulin A (IgA) nephropathy rather than APSGN. 9. Ac Nephritic Syndrome Clinical Presentation Classic Triad Haematuria Edema Hypertension 40 % Classical 95% have atleast 2 of these Hematuria This is present universally. In 30% of cases, gross hematuria is present. Edema Edema is present in 80-90% of cases, and it is the presenting complaint in 60% of cases. Reduced blood flow to the glomerulus that manifests as low fractional excretion of sodium and concentrated urine. This salt and water retention leads to edema. 10. Ac Nephritic Syndrome Clinical Presentation Hypertension Hypertension occurs in 60-80% of cases and is more common among elderly individuals. In 50% of cases, the hypertension can be severe; however, more often it is transient, with normalization of blood pressure upon restoration of the glomerular filtration rate, loss of edema, and normalization of plasma volume. If hypertension persists, it is more indicative of the progression to a more chronic stage or that the disease is not poststreptococcal glomerulonephritis. Hypertension is thought to be the result of excessive salt and water retention. Hypertensive encephalopathy occurs in no more than 5-10% of patients. Usually, clinical improvement occurs without any neurological sequelae. Oliguria This is present in 10-50% of cases, and, in 15%, urine output is less than 200 mL. Oliguria is indicative of the severe crescentic form of the disease. It is often transient, with diuresis occurring within 1-2 weeks. 11. Acute Nephritic Syndrome 12. D/D Membranoproliferative glomerulonephritis (MPGN) The presentation of MPGN may be indistinguishable initially from PSGN. It typically presents with hematuria, hypertension, proteinuria, and hypocomplementemia following an upper respiratory infection. However, patients with MPGN continue to have persistent nephritis and hypocomplementemia beyond four to six weeks and possibly a further elevation in serum creatinine. In contrast, patients with PSGN typically have resolution of their disease and a return of normal C3 and CH50 levels IgA nephropathy Patients with IgA nephropathy often present after an upper respiratory infection, similar to the presentation of patients with PSGN. Potential distinguishing features from PSGN include a shorter time between the antecedent illness and hematuria is (less than 5 versus more than 10 days in PSGN) and a history of prior episodes of gross hematuria since recurrence is rare in PSGN Lupus nephritis and Henoch-Schnlein purpura (IgA vasculitis) nephritis share similar features to PSGN. However, extrarenal manifestations of the underlying systemic diseases and laboratory testing should differentiate them from PSGN.. 13. Ac Nephritic Syndrome Work Up RFT'S :- This reflects the decrease in the glomerular filtration rate that occurs in the acute phase. The elevations are usually transient. Most common in APSGN. Prolonged Elevation S/O other causes. Patients who have the crescentic form of glomerulonephritis( RPGN) have rapid deterioration and, often, incomplete recovery of renal function 14. Ac Nephritic Syndrome Work Up Urinalysis Results are always abnormal. Hematuria and proteinuria are present in all cases. Urine sediment has red blood cells, red blood cell casts, white blood cells, granular casts, and, rarely, white blood cell casts. Dysmorphic red blood cells indicative of glomerular hematuria can usually be detected by performing phase-contrast microscopy. Red blood cell casts are best detected in first, early-morning urine specimens examined by the physician immediately after the patient voids. Hematuria usually resolves within 3-6 months but may persist as long as 18 months. Microscopic hematuria may be present in patients in whom the disease has otherwise clinically resolved. Proteinuria may be mild or so severe that it causes nephrotic syndrome. Approximately 5-10% of patients with APSGN have nephrotic-range proteinuria. Proteinuria usually disappears in 6 months. A mild increase in urinary protein excretion is present in 15% at 3 years and 2% at 10 years. Patients with nephrotic-range proteinuria in the acute phase or persistent heavy proteinuria have a worse prognosis. This is often associated with an evolution to a garlandlike pattern of immune deposits as the disease progresses. 15. Phase contrast micrograph showing dysmorphic red cells in urine sediment Scanning electron micrograph showing dysmorphic red cells in urine sediment Photomicrograph of urine sediment with a red cell cast 16. Evidence of preceding streptococcal infection Antibody titers to extracellular products of streptococci are positive in more than 95% of patients with pharyngitis and 80% of patients with skin infections. The antistreptolysin (ASO), antinicotinamide adenine dinucleotidase (anti-NAD), antihyaluronidase (AHase), and antiDNAse B are commonly positive after pharyngitis, and antiDNAse B and AHase titers are more often positive following skin infections. ASO titers are frequently used to document streptococcal infection, but a more sensitive test is the streptozyme test, which tests antibodies to ASO, anti DNAse B, AHase, and anti-NAD. Studies suggest that the relatively unavailable antizymogen titer test is superior to both antiDNAse B and ASO titers. In general, the antibody titers are elevated at 1 week, peak at 1 month, and fall toward preinfection levels after several months. Ac Nephritic Syndrome Work Up 17. Understanding Serology In Ac Nephritis 18. Ac Nephritic Syndrome Work Up UltraSound Renal ultrasound images usually reveal normal-sized kidneys bilaterally. Nephromegaly/ Echogenic Kidneys rarely seen and is S/O Ac Inflamation Renal Biopsy APSGN is often a clinical diagnosis and requires the detection of glomerulonephritis and evidence of preceding streptococcal infection. Atypical features in the early phase that suggest the need for renal biopsy include the following: Absence of the latent period between streptococcal infection and acute glomerulonephritis Anuria Rapidly deteriorating renal function Normal serum complement levels No rise in antistreptococcal antibodies Extrarenal manifestations of systemic disease-- S/O LUPUS NEPHRITIS No improvement or continued decrease in the glomerular filtration rate at 2 weeks Persistence of hypertension beyond 2 weeks 19. APSGN- LM STUDY 20. APSGN- EM Humps 21. Necrosis 22. Cellular Crescent Glomerulus 23. Ac Nephritic Synd Rx Symptomatic therapy is recommended for patients with Ac Nephritic Synd, and it should be based on the clinical severity of the illness. The major goal is to control edema and blood pressure. During the acute phase of the disease, restrict salt and water. If significant edema or hypertension develops, administer diuretics. Loop diuretics increase urinary output and consequently improve cardiovascular congestion and hypertension. For hypertension not controlled by diuretics, usually calcium channel blockers or angiotensin-converting enzyme inhibitors are useful. For malignant hypertension, intravenous nitroprusside or other parenteral agents are used. Indications for dialysis include life-threatening hyperkalemia and clinical manifestations of uremia. Restricting physical activity is appropriate in the first few days of the illness but is unnecessary once the patient feels well. Steroids, immunosuppressive agents, and plasmapheresis are not generally indicated.