1. Glomerulonephritis and Hematuria Dr. Abdulkadhim Imran Moosa Pediatrics Consultant

2. ETIOLOGY AND EPIDEMIOLOGY A child with gross hematuria requires prompt evaluation. 1. careful history 2.physical examination 3.urinalysis A-Red urine with no blood on a dipstick implies that the child has ingested foods, medications, or chemicals that led to the color change. In infants, urate crystals, which are orange red, can be seen on diapers

3. urate crystals

5. B-Red urine, blood on dipstick, but no blood on microscopy. 1.Hemoglobinuria may result from acute intravascular hemolysis 2.Myoglobinuria results from rhabdomyolysis secondary to crush injury

7. C-Red urine, blood on dipstick and microscopy, but no RBC casts suggests urinary tract bleeding from a site beyond the renal tubules.

8. D-Red urine, blood on dipstick and microscopy,altered RBC morphology with RBC casts, suggests one of a variety of glomerular diseases. 1.Immunologic injury (post streptococcal acute glomerulonephritis, [PSAGN] 2.inherited disease (Alport syndrome ) 3.vascular injury (acute tubular or cortical necrosis).

9. The presence of this red blood cell cast in on urine microscopic analysis suggests a glomerular or renal tubular injury.

10. These are granular casts, with a roughly rectangular shape.

11. Children who have hematuria, with casts and proteinuria less than 1 g/m2//day, are considered to have nephritis. The absence of cast &normal RBC morphology does not exclude glomerular etiology.

12. Glomerulonephritis Associated with Infections Poststreptococcal Acute Glomerulonephritis PSAGN characterized by the sudden onset of 1.Gross hematuria, 2. Edema, 3.Hypertension, 4. Renal insufficiency. PSAGN is one of the most common glomerular causes of gross hematuria in children.

13. Pathogenesis PSAGN is the most common form Immune-mediated inflammation mechanism for proliferative glomerulonephritis PSAGN usually follows a streptococcal pharyngitis or impetigo. An immunologic reaction to the bacteria, mediated by activation of complement, leads to a proliferative glomerulonephritis.

14. Post streptococcal glomerulonephritis is most common in children aged 5–12 yr and uncommon before the age of 3 yr. Boys are more frequently affected. Post streptococcal glomerulonephritis commonly follows streptococcal pharyngitis during cold weather months and streptococcal skin infections or pyoderma during warm weather months Crowded conditions, poor hygiene, malnutrition, and intestinal parasites may result in epidemic outbreaks

16. Clinical Manifestations PSAGN is associated with hematuria (gross in 65% of cases), edema (75% of cases), and hypertension (50% of cases). Acute renal insufficiency also can occur. Manifestations develop 5 to 21 days (10 days on average) after nephritogenic streptococcal infections (pharyngitis or impetigo) Tea-colored or cola-colored urine are the most common clinical presentations.

17. Renal insufficiency and consequent oliguria and hypertension may lead to complications such as heart failure and encephalopathy.

18. The diagnosis of PSAGN is based on the findings of hematuria with cast proteinuria, edema, and hypertension.

19. D.Diagnosis 1.UTI is the most common identifiable diagnosis made in a child with gross hematuria 2.Hematuria without casts is seen in sickle cell trait or disease, after strenuous exercise, and after renal trauma. 3.Hypercalciuria is an important cause of isolated hematuria in children 4.Coagulopathies can lead to hematuria. 5.Urolithiasis is a cause of painful hematuria

20. D.D 6-Structural abnormalities of the urinary tract 7-Malignant tumors (Wilms tumor in the kidney 8-Obstruction, cystic disease, and trauma may be accompanied by hematuria 9-Benign familial hematuria(Thin Basement Membrane Disease ), is a common, nonprogressive, usually autosomal dominant disorder, often accompanied by thinning of the glomerular basement membrane on electron microscopy. Microscopic hematuria is often initially observed during childhood and may be intermittent. Episodic gross hematuria can also be present, particularly after a respiratory illness. Other family members also have hematuria.

21. 10-The most common form of chronic GN in children is IgA nephropathy (IgA GN), which often presents with microscopic hematuria or recurrent gross hematuria shortly after onset of upper respiratory infection. Biopsy reveals a focal proliferative glomerulonephritis. The course of IgA GN is usually benign, and occurs more frequently in boys and in school age children and young adults. IgA GN may progress to end-stage renal disease (ESRD) in up to 30% of children, particularly in patients with proteinuria or renal insufficiency at presentation. There are now promising results with chronic steroid therapy and anti-inflammatory strategies (fish oil, vitamin E) in IgA GN. (Normal C3),IgA is elevated 20%

22. 11-Alport syndrome,microscopic hematuria +bilateral neurosensory deafness +progressive renal failure during adolescence and young adulthood, particularly in males. +familial. 12-Henoch-Schönlein Purpura Nephritis 13- Glomerulonephritis Associated with Systemic Lupus Erythematosus

23. LABORATORY STUDIES 1.G.U.E, hematuria, mild to moderate proteinuria, concentrated urine, and the presence of casts, particularly granular and RBC casts. 2.The BUN and serum creatinine may be transiently elevated 3.elevated titers of antistreptococcal antibodies 4.Serum C3 and CH 50 levels are depressed within 2 weeks of the occurrence of the disease. C4 levels remain normal, indicating activation of the alternate complement pathway.

24. The C3 returns to normal by 6 to 8 weeks. Hypocomplementemia persisting beyond 8 weeks or normal C3 at the start suggest another condition, most likely mesangiocapillary (also called membra- noproliferative) glomerulonephritis. Serum IgG and IgM are usually elevated.

25. Ultrasound, CT, and rarely IV pyelography of the urinary tract are the most common imaging modalities used in the evaluation of hematuria.

26. Renal biopsy should be considered only in the presence of 1. Acute renal failure, 2.Nephrotic syndrome, 3.Absence of evidence of streptococcal infection, 4. Normal complement levels C3(1 st 2 mo ). 5.Hematuria and proteinuria, diminished renal function, and/or a low C3 level persist more than 2 mo after onset.

27. COMPLICATIONS 1)hypertensive encephalopathy in 10% of cases. 2)heart failure, 3) hyperkalemia, 4) hyperphosphatemia, 5)hypocalcemia, 6)acidosis, 7) seizures, and uremia.

28. Therapy 1.Dietary sodium restriction 2.Diuretics 3.Antihypertensive agents 4.Although 4.Although a 10-day course of systemic antibiotic therapy with penicillin is recommended to limit the spread of the nephritogenic organisms, antibiotic therapy does not affect the natural history of glomerulonephritis

29. Prognosis And Prevention PSAGN is a relatively benign disease in children. Complete recovery occurs in more than 95% of children with acute post streptococcal glomerulonephritis Treating the streptococcal infection does not prevent PSAGN IgA nephropathy results in a variable rate of chronic renal failure,Recurrence of IgA deposits in transplanted kidneys is often observed

30. HUS Hemolytic Uremic Syndrome ETIOLOGY AND EPIDEMIOLOGY HUS is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal injury It is an important cause of acute renal failure (ARF) in children. The most common type, D+HUS, is associated with a prodromal diarrheal illness and may be sporadic, epidemic, or endemic

31. . The disease typically occurs in children between 6 months and 4 years of age. Verotoxins (VTs) have been implicated in most D+HUS, especially the Shiga- like toxin from Escherichia coli O157:H7. D-HUS, familial cases, and sporadic HUS have poorer outcomes.

32. CLINICAL MANIFESTATIONS Classic D+HUS typically begins as gastroenteritis, often bloody, followed in 7 to 10 days by weakness, lethargy, irritability, and oliguria/anuria.case to case transmission is not common feature. Physical examination reveals irritability, pallor, edema, petechiae, and occasionally hepatosplenomegaly. Dehydration is often present; however, some children have volume overload. Hypertension may be due to volume overload or renin.

33. CLINICAL MANIFESTATIONS..detto The diagnosis is supported by the presence of microangiopathic hemolytic anemia, thrombocytopenia, and renal involvement (hematuria, renal insufficiency). Seizures may indicate central nervous system (CNS) involvement and occur in 20% of cases.

34. Diagnostic Studies Peripheral blood smear reveals schistocytes, helmet and burr cells, and fragmented erythrocytes, (intravascular hemolysis). Fragmented red cells on the blood film is not pathognomonic (DIC, TTP, DRUG,VALVE PROSTHESIS).DICTTP Evidence for disseminated intravascular coagulation is rarely present. The reticulocyte count is elevated and plasma haptoglobin is low.

35. Schistocyte/helmet cells

36. Coombs test is negative. Leukocytosis is common. Urinalysis typically reveals hematuria, proteinuria, and casts. Stool can be cultured to identify VT- producing E. coli strains. Tests for demonstration of VT in stool are now also available.

37. Treatment Therapy for HUS is supportive and includes volume repletion, control of hypertension, and early dialysis when indicated. Red blood cell transfusions are provided as needed but platelet transfusions are beneficial only during active hemorrhage. Antibiotics for the prodromal diarrhea may increase the risk of developing HUS. Antidiarrheal agents prolong exposure to VT- producing bacteria and should be avoided

38. Prognosis Prognosis. Most children (>95%) survive the acute phase; more than 50% recover normal renal function. D+HUS has the best prognosis. D-HUS, familial cases, and sporadic HUS have poorer outcomes.

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