5: NEPHROLOGY-1.pdf

2. Red Flags in Renal Disease Glomerular Diseases (Nephritic/ Nephrotic Syndrome) UTI Acute VS Chronic Kidney Disease Pediatric Nephrology 101 What Every Medical Student Should Know • Recognize Red Flags in Renal Disease • Understand the pahophysiology of common pediatric renal diseases • Correlate and interpret the clinical and laboratory findings • Formulate a differential diagnosis • Plan the appropriate management • Recognize complications associated with pediatric renal disease as well as its prognosis

3. Red Flags in Renal Disease Pediatric Nephrology 101

4. • - the passage of a larger amount of urine than normal • daily urine output exceeding 2L in school-aged children is unusual • indicates decrease in concentrating ability • important to distinguish polyuria from frequency of micturition Lorem ipsum dolor sit Dolor sit amet conscter pod Consectetur adipiscing Pediatric Nephrology 101 Red Flags in Renal Disease POLYURIA

5. • healthy neonate Is oliguric for the first 2–3 days of life until the onset of the postnatal diuresis • 92% - 1st 24 h of life • Almost ALL in the first 48 h • Oliguria is defined a urine output of less than 500 ml/24 h/ 1.73 m2 • The most common cause - intravascular volume depletion • Other Causes • intrinsic • obstructive Red Flags in Renal Disease Pediatric Nephrology 101 OLIGO/ANURIA

6. Lorem ipsum dolor sit Dol r pod Con or sit amet conscte sectetur adipiscing DYSURIA • Symptoms specific to the urinary tract • hematuria • discharge • malodorous urine • frequency • urgency • refusal to void • new-onset nocturnal enuresis • daytime incontinence • pain on urination • inflammation, irritation, or obstruction of the urinary tract • Associated with • UTIs • urethritis • chemical or traumatic irritation • Possible Causes • exposure to irritants to the mucosal lining of the urethra/bladder • bladder bowel dysfunction • trauma • sexually transmitted infection • A family history of nephrolithiasis Red Flags in Renal Disease Pediatric Nephrology 101

7. HYPERTENSION Flynn JT, Kaelber DC, Baker-Smith CM, et al. Clinical practice guideline for screening and management of high blood pressure i n children and adolescents. Pediatrics. Red Flags in Renal Disease Pediatric Nephrology 101

8. HYPERTENSION Flynn JT, Kaelber DC, Baker-Smith CM, et al. Clinical practice guideline for screening and management of high blood pressure i n children and adolescents. Pediatrics. Red Flags in Renal Disease Pediatric Nephrology 101 • 1-5% prevalence in children • secondary to renal, cardiovascular, endocrine • part of spectrum of essential hypertension • 3 most common symptoms • headache, difficulty sleeping and tiredness • routine BP screening starting age 3 years

9. Lorem ipsum dolor Dolor sit amet cons mecter Consectetur adipis + Free plan EDEMA • a major clinical manifestation of ECF volume expansion • Nephrotic Syndrome • proteinuria • hypoalbuminemia • hyperlipidemia • edema first evident as swelling of the periorbital region more generalized edema develops in a gravity dependent distribution • Acute Nephritic Syndrome / acute renal impairment as a result of failure of salt and water excretion • peripheral edema • intravascular volume expansion • hypertension • pulmonary edema Red Flags in Renal Disease Pediatric Nephrology 101

10. PALLOR • Anemia is one of the most common complications of CKD during childhood • K/DOQI Anemia Management guidelines defined anemia as a hemoglobin value less than 11 gm/dl in pre-pubertal patients with CKD Red Flags in Renal Disease Pediatric Nephrology 101

11. PROTEINURIA Significant quantities of protein in the urine will result in it becoming frothy. • represents significant renal disorder • Dipstick analysis followed by formal quantification of protein content Red Flags in Renal Disease Pediatric Nephrology 101

12. Lorem ipsum dolor sit Dolor sit amet conscter pod Consectetur adipiscing HEMATURIA • presence of RBCs in urine • Microscopic Hematuria 5 red blood cells (RBCs)/mL of urine in a counting chamber or 2 RBCs/high-power field (hpf) of urinary sediment • Chronic medical problems, multisystemic disease - SLE, Wegener’s granulomatosis, Goodpasture syndrome • History of trauma - Bleeding in the Urinary Tract • Recent Throat/Skin Infection - PSGN • Presence/Family history of hearing loss - Alport’s Syndrome • Presence of purpuric rashes over the lower extremities - HSP • Hypertension - Acute Nephritis • History of fever, flank pain, dysuria - UTI Red Flags in Renal Disease Pediatric Nephrology 101

13. Any symptom can be a presentation of kidney disease Complete History and PE is key One should be familiar with the modes of presentation of different renal conditions and should have a high index of suspicion of renal disease Pediatric Nephrology 101 Red Flags in Renal Disease

14. Pediatric Nephrology Lecture Series Maria Dalla J. Dosado, MD

15. Bedside ROUNDS

16. BED1 4 year old male edema for 2 weeks frothy urine cough 1 week duration Laboratorie s Normal CBC Serum albumin 20mg/dL Urinalysis protein +3, RBC3-5, WBC 4-5, bacteria few

17. Normal Protein Excretion Avner, et al, Pediatric Nephrology 2007 DOI 10.1007/978-3-662-43596-0

18. Protein in Urinalysis Urinalysis Protein Trace <0.3g/dL +1 <1g/dL +2 1g-3g/dL +3 3-20g/dL +4 >20g/dL Avner, et al, Pediatric Nephrology 2007 DOI 10.1007/978-3-662-43596-0

19. T ypes of Proteinuria Glomerular proteinuria increased filtration of protein across the glomerular membrane most commoncause of proteinuria in children ~glomerular disease ~other non-pathologic conditions such as orthostatic proteinuria, fever, and excessive exercise Avner, et al, Pediatric Nephrology 2007 DOI 10.1007/978-3-662-43596-0

20. T ypes of Proteinuria T ubular proteinuria reduced reabsorption of freely filtered LMWProteins Overflow proteinuria due to increased levels of low molecular weight proteins in the plasma ~ overwhelm tubular reabsorptive capacity Avner, et al, Pediatric Nephrology 2007 DOI 10.1007/978-3-662-43596-0

21. Conditions with Proteinuria Exercise Fever Orthostatic Dehydration Drugs Chemotherap y Heavy metals Antibiotics Medical conditions Hemolysis Rhabdomyolysis Multiple myeloma Amyloidosis Kidney diseases Glomerulonephritis T ubular diseases Reflux nephropathy Diabetes Mellitus Avner, et al, Pediatric Nephrology 2007 DOI 10.1007/978-3-662-43596-0

22. Patient A DIAGNOSIS

23. UnderlyingAbnormality in NEPHROTIC SYNDROME Increased permeability of the glomerular capillary wall • massive proteinuria • hypoalbuminemia

24. UnderlyingAbnormality in NEPHROTIC SYNDROME Podocyte - epithelial cell - foot processes - slit diaphragms - nephrin - podocin - CD2AP - α-actinin 4 Podocyte Functions • structural support of the capillary loop • major component of the glomerular filltration barrier to proteins • involved in synthesis and repair of the glomerular basement membrane

25. UnderlyingAbnormality in NEPHROTIC SYNDROME Podocyte injury or genetic mutations of genes produc- ing podocyte proteins may cause nephrotic-range proteinuria • foot process effacement of the podocyte • decrease in number of functional podocytes • altered slit diaphragm integrity increased protein “leakiness” across the glomerular capillary wall into the urinary space

26. Immune System ? contributes to the overall pathogenesis of the nephrotic syndrome *MCNS occur after viral infections *MCNS in children with HL and T cell lymphoma *use of immunosupressive agents in cases of SRNS

27. Causes of Nephrotic Syndrome

29. Avner, et al, Pediatric Nephrology 2007 DOI 10.1007/978-3-662-43596-0 Nephrotic Syndrome History insidious onset of edema progressing to frank anasarca Decreased urine output OtherSymptoms-diarrhea,abdominal pain,poorappetite and irritability

30. Avner, et al, Pediatric Nephrology 2007 DOI 10.1007/978-3-662-43596-0 Nephrotic Syndrome Clinical Consequences • Edema • Hyperlipidemia • Increased susceptibility to infections • Hypercoagulability

31. Volume Expanded (Overfill) ( FeNa >0.2 , Urine K index >0.6 ) Volume Contracted (Underfill) (FeNa<0.2, Urine K index <0.6)

32. Avner, et al, Pediatric Nephrology 2007 DOI 10.1007/978-3-662-43596-0 Nephrotic Syndrome:Work Up Low Serumalbumin HighSerumCholesterol CBC- Hemoconcentrated KUBUTZ - normalorenlargedkidneys Urinalysis - 3+ urineproteindipstick - MicroscopicHematuria Randomspoturine protein - >2000 mg/g (200mg/mmol) 24 hourtotal protein excretion ->40mg/m2/hr Renal Biopsy

34. Avner et al, Pediatric Nephrology 2007 Management cause Anti-proteinuric agents ImmunosuppreS u sp sp o ir ot i v neTreatment Antibiotics prednisone or prednisolD on iue retics Dependass o i n n g u l n e d d e a r l i y l y i n d g o s eof 60 m A g l b / m u m 2 i / n d i n a f y u s o i o r n 2 mg/kg/da (A yCE inhibitors, ARBs) maximum of 60 mg daily for 4-6 wk Withdrawal of offending agf e o n llt o s wed by alternate-day prednisone (starting at 40 mg/m2 qod or 1.5 mg/kg qod) for a period ranging from 8 wk to 5 mo,with tapering of the dose

35. Avner et al, Pediatric Nephrology 2007 Management Depends on underlying cause Antibiotics A lbum in infusion Anti-proteinuric agents ResponseSupportiveT reatment the attainment of remission withD i iu nr e t ti c hs einitial 4 wk of corticosteroid therapy Remissio ( n ACE inhibitors, ARBs) Witu hd ri rn aw ea p lr o o fto e fi fn en: dc in r g eatinine ratio of <0.2 or <1+ p r o a t e g i e n n t o s n urine dipstick for 3 consecutive days

36. Management Referral to Nephrology Frequent Relapsers Steroid Dependent Steroid Resistant Avner et al, Pediatric Nephrology 2007

37. Avner et al, Pediatric Nephrology 2007 Management cause agents Antibiotics Diuretics Albumin infusion Anti-proteinuric agents (ACE inhibitors, ARBs) Alternative Therapies to Corticosteroids in the Treatment of Nephrotic Syndro S m up e portiveTreatment • C D y e c p l e o n p d h o s s o p n h a u m n d i d e e r l y i n g • Calcineurin Inhibitors •W M it y h cd or p a h w en a o llo at feoffending • Rituximab

39. Bed 2 6yo Male URTI 2 weeks prior to consult facial edema and dark colored urine blood pressure = 120/80mm/Hg Urinalysis = RBCTNTC/WBC8-10/ Protein +4 80% dysmorphic RBCon phase constrast microscopy

40. Diagnosis? A.Acute Hemorrhagic Cystitis B.Minimal Change Nephrotic Syndrome C.Post Infectious Glomerulonephritis D.UricAcid Urolithiasis

41. Clinical Approach to a child with Hematuria Confirm the presence of hematuria Differentiate glomerular from non-glomerular causes Detailed history and physical examination to determine the underlying cause Assess severity and associated complications of the hematuria

42. HEMA TURIA Hematuria presence of RBCs in urine Microscopic Hematuria 5 red blood cells (RBCs)/mL of urine in a counting chamber or 2 RBCs/high-power field (hpf) of urinary sediment

43. Dela Cena, 2017 NKTI PNAA 5th Symposium

44. HISTORY & PE PROBABLE DISEASES Recent throat infection, skin infection Post -Infectious Glomerulonephritis Presence/Family history of hearing loss Presence of purpuric rashes over the lower extremities Hypertension History of fever, flank pain, dysuria Chronic medical problems, multisystemic disease History of trauma Alport’s Syndrome Henoch-Schonlein Purpura Acute nephritis/ nephritic syndrome UTI SLE, Wegener’s granulomatosis, Goodpasture syndrome Bleeding in urinary tract Causes of Hematuria Dela Cena, 2017 NKTI PNAA 5th Symposium

45. Glomerular vs Non- glomerular Hematuria • • Evaluation of hematuria in children. Kevin E. C. MeyersPublished 2004 in The Urologic clinics of North America

46. Acute Nephritic Syndrome • glomerular hematuria • hypertension • edema • moderate proteinuria

47. Hematuria &Acute Nephritic Syndrome History acute onset of edema and dark colored urine *oliguria Physical Examination Hypertension due to fluid overload Localized periorbital /facial edema

48. Hematuria &Acute Nephritic Syndrome Pertinent Laboratory • ** 5RBCs/HPF in the urine w/ CG casts • Dysmorphic RBCs in phase contrast microscopy • Non-Nephrotic Range Proteinuria

49. Hematuria &Acute Nephritic Syndrome Complications • Hypertensive Encephalopathy • Congestive Heart Failure • Acute Kidney Injury • Rapidly Progressive Glomerulonephritis

50. Hematuria &Acute Nephritic Syndrome -Differential Diagnosis- Post Streptococcal Glomerulonephritis IgA nephropathy HSP Nephritis

51. Hematuria &Acute Nephritic Syndrome Post Streptococcal Glomerulonephritis immune complex mediated process for Group A Beta Hemolytic Streptococcus *gross hematuria ~2-4 weeks post respiratory or skin infection *low C3 *+ /-ASO/ Anti DNAse

52. Hematuria &Acute Nephritic Syndrome Ig A Nephropathy recurrent episodes of gross hematuria 1-2 days after a viral respiratory infection or GI infection *absent latent phase *mesangial IgA deposits on renal biopsy initially considered a benign condition spontaneous remission in IgAN patients with minor glomerular abnormalities or focal mesangial proliferation 20–50 % of adults would ultimately progress to end-stage renal failure

53. Hematuria &Acute Nephritic Syndrome Henoch Schonlein Purpura Nephritis within 3 months of onset of a palpable rash, joint pains and GI complaints *Hallmark - HEMATURIA ** 8 0 % will manifest in 4 weeks *** 9 5 % within 3 months

54. Management Depends on underlying cause Supportive (PSGN) Fluid and salt limitation Diuretics Anti-hypertensive drugs Immunosuppression Nephrology Referral

55. Hematuria &Acute Nephritic Syndrome:PSGN- Patient Follow Up Gross Hematuria - 3 weeks C3 - 2-3 months Proteinuria - 3-6 months Microscopic Hematuria - 1 year

56. Diagnosis Post Infectious Glomerulonephritis

57. Glomerular Diseases in Childhood

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