1. Copyright © 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 25 Disorders of Renal Function Dory Roedel Ferraro, DNP, ANP-BC, CBN College of New Rochelle School of Nursing

2. Copyright © 2015 Wolters Kluwer All Rights Reserved Chapter Outline Congenital and hereditary disorders of the kidney Disorders of glomerular function Tubulointerstitial disorders Obstructive disorders Malignant neoplasms

3. Copyright © 2015 Wolters Kluwer All Rights Reserved Congenital and Hereditary Disorders Kidney development begins in 5 th week of gestation Urine formation begins at the 9 th week and is excreted in the amniotic cavity and is the main component of amniotic fluid 10% of all people are born with potentially significant malformations of the urinary system; most acquired defects during embryonic development

4. Copyright © 2015 Wolters Kluwer All Rights Reserved Disorders of Kidney Development Renal agenesis –complete failure of an organ to develop –Bilateral agenesis occurs 1 in 3000 births –Unilateral agenesis is compatible with life and is usually a coincidental finding Renal hypoplasia –Kidney(s) small is size with fewer nephrons and calyces –Can lead to renal failure if bilateral

5. Copyright © 2015 Wolters Kluwer All Rights Reserved Disorders of Kidney Development Renal dysplasia –Maldifferentiated structure in all or part of the kidney –MDKD-multicystic dysplastic kidney disorder generally unilateral Hypertension and Wilms tumor occurs in 1 in 333 cases Annual follow-up with BP and ultrasound is recommended Alteration in position and form –Horseshoe kidney-the upper and lower poles of the kidneys are fused

6. Copyright © 2015 Wolters Kluwer All Rights Reserved Cystic Diseases of the Kidney Genetic –Autosomal dominant polycystic kidney disease (inherit one defective gene from one parent) –Autosomal recessive polycystic kidney disease (inherit two defective genes, one gene from each parent) –Nephronophthisis –Medullary cystic kidney disease Acquired –Simple cysts –Acquired form of renal cystic disease

7. Copyright © 2015 Wolters Kluwer All Rights Reserved Genetic Cystic Diseases Autosomal dominant polycystic kidney disease (ADPKD) Inherit one defective gene from one parent Most common of all inherited kidney diseases Characterized by multiple expanding cysts that ultimately destroy the kidney Diagnosed by ultrasound and screening of family members Treatment is supportive and aimed at delaying disease progression Autosomal recessive polycystic kidney disease (ARPKD) inherit two defective genes, one gene from each parent

8. Copyright © 2015 Wolters Kluwer All Rights Reserved Nephronopthisis and Medullary Cystic Kidney Disease Small and shrunken kidneys with multiple cysts Progresses to chronic kidney disease

9. Copyright © 2015 Wolters Kluwer All Rights Reserved Disorders of Glomerular Function Acute nephritic syndrome Rapid progressive glomerulonephritis Nephrotic syndrome IgA nephropathy Hereditary nephritis Chronic glomerulonephritis Glomerular lesions in systemic disease

10. Copyright © 2015 Wolters Kluwer All Rights Reserved Glomerular Damage Proliferative: number of cells increase. Membranous: glomerular basement membrane thickens. Sclerotic: amount of extracellular matrix increases. All can decrease the efficiency of filtration. Allow blood cells, lipids, or proteins to pass into the urine.

11. Copyright © 2015 Wolters Kluwer All Rights Reserved Types of Glomerular Diseases Nephritic syndromes – proliferative inflammatory response Nephrotic syndromes – increased permeability of the glomerulus Mixed nephritic and nephrotic syndromes Definitive diagnosis requires renal biopsy

12. Copyright © 2015 Wolters Kluwer All Rights Reserved Acute Nephritic Syndrome Acute inflammatory process that occludes the glomerular capillary lumen and damages the capillary wall Primary (acute postinfectious glomerulonephritis) Secondary complicating disorder of systemic disease (SLE) Characterized by sudden onset of hematuria, proteinuria, diminished GFR, oliguria, signs of impaired renal function ECF accumulation, edema, hypertension

13. Copyright © 2015 Wolters Kluwer All Rights Reserved Acute Postinfectious Glomerulonephritis Occurs after infection with certain strains of group A β- hemolytic streptococci, staph infections, viruses (measles, mumps, chicken pox) Caused by deposition of immune complexes Rare in industrialized world Excellent prognosis if treated Rarely causes CKD

14. Copyright © 2015 Wolters Kluwer All Rights Reserved Rapidly Progressive Glomerulonephritis Clinical syndrome characterized by signs of severe glomerular injury May be caused by immunologic disorders Goodpasture Syndrome- an uncommon and aggressive form of rapidly progressive glomerulonephritis

15. Copyright © 2015 Wolters Kluwer All Rights Reserved Nephrotic Syndrome A constellation of clinical findings that result from an increase in glomerular permeability and loss of plasma proteins in the urine Characterized by massive proteinuria and lipiduria Hypoalbuminemia, generalized edema and hyperlipidemia At risk for thrombotic complications (DVT, PE)

16. Copyright © 2015 Wolters Kluwer All Rights Reserved Nephrotic Syndrome

17. Copyright © 2015 Wolters Kluwer All Rights Reserved Membranous Glomerulonephritis Most common cause of primary nephrosis in adults Characterized by diffuse thickening of the glomerular basement membrane due to deposition of immune complexes Idiopathic Associated with autoimmune diseases, infections and metabolic disorders

18. Copyright © 2015 Wolters Kluwer All Rights Reserved Focal Segmental Glomerulonecrosis Characterized by sclerosis Accounts for 30% of primary nephrotic syndrome in adults More common in AA

19. Copyright © 2015 Wolters Kluwer All Rights Reserved IgA Nephropathy (Berger Disease) Primary glomerulonephritis Characterized by the presence of glomerular IgA immune complex deposits which cause inflammation Typically asymptomatic; usually discovered during routine physical May present with gross hematuria

20. Copyright © 2015 Wolters Kluwer All Rights Reserved Glomerular Lesions Associated with Systemic Disease Systemic lupus erythematous glomerulonephritis –Lupus nephritis –Renal involvement most common complication of SLE –Routine screening for hematuria and proteinuria in SLE patients Diabetic glomerulosclerosis

21. Copyright © 2015 Wolters Kluwer All Rights Reserved Diabetic Nephropathy Major cause of CKD and the most common cause of renal failure treated by organ replacement Occurs in both types (1 and 2) Widespread thickening of the glomerular capillary basement membrane Elevations in blood glucose cause an increase in GFR and glomerular pressure that lead to enlargement of glomerular capillary pores Clinical manifestations: GFR, microalbuminuria (Iimp. Predictor of future diabetic nephropathy) Changes may be reversed by careful regulation of blood glucose, ACE inhibitors, cessation of smoking and control of blood pressure

22. Copyright © 2015 Wolters Kluwer All Rights Reserved Scenario A woman with diabetes mellitus: Has severe edema and frothy, cola-colored urine Has difficulty breathing, with crackles in both lungs Just finished a course of antibiotics for strep throat Is taking corticosteroids for lupus-related arthritis Question: What are three reasons for her renal problems?

23. Copyright © 2015 Wolters Kluwer All Rights Reserved Scenario (cont.) A woman: Has diabetes mellitus and lupus Recently had strep throat Has severe edema and frothy, cola-colored urine Question: The doctor says the only way to determine what has caused her glomerular disease is a renal biopsy. Why?

24. Copyright © 2015 Wolters Kluwer All Rights Reserved Scenario (cont.) Urinalysis show that she is producing urine –With 500 mg protein/day –Containing blood and RBC casts –With high level of K + Blood tests show –Hypoalbuminemia and slightly decreased K + She has borderline hypertension Question: Does she have nephritic syndrome or nephrotic syndrome?

25. Copyright © 2015 Wolters Kluwer All Rights Reserved Scenario (cont.) Urinalysis show that she is producing urine –With 500 mg protein/day –Containing blood and RBC casts –With high level of K + Blood tests show –Hypoalbuminemia and slightly decreased K + She has borderline hypertension Question: Does she have nephritic syndrome or nephrotic syndrome? (Acute postinfectious glomerulonephritis)

26. Copyright © 2015 Wolters Kluwer All Rights Reserved Nephritic vs. Nephrotic Syndrome Nephritic Syndrome Loss of blood Hematuria Red cell casts Low urine volume Mild hypertension Proteinuria (mild) Nephrotic syndrome Loss of protein proteinuria Urine is frothy Albumin is lost in urine Swelling around eyes and in ankles Hyperlipidemia

27. Copyright © 2015 Wolters Kluwer All Rights Reserved Nephritic/Nephrotic Syndrome in Differential Diagnosis Nephritic Postinfectious glomerularnephritis IgA nephropathy Rapidly progressive glomerulonephritis Nephrotic Minimal change glomerulonephritis Focal segmental Glomerulosclerosis Membranous glomerulonephritis Secondary causes –SLE –DM –Hep B and C –HIV

28. Copyright © 2015 Wolters Kluwer All Rights Reserved Tubular and Interstitial Disorders Acute tubular necrosis (Chapter 26) Tubulointerstitial nephritis (Acute or chronic inflammation of tubules) Pyelonephritis –Acute pyelonephritis –Chronic pyelonephritis Drug-related nephropathies

29. Copyright © 2015 Wolters Kluwer All Rights Reserved Acute Pyelonephritis Acute suppurative inflammation of the kidney caused by inflammation as a result of bacterial infection Escherichia coli causative agent in 80% cases Complicated –Occurs in the presence of structural or functional abnormalities (outflow obstruction, pregnancy, neurogenic bladder) –Predisposing medical conditions Uncomplicated –Most commonly seen in young women –Abrupt onset with shaking chills, fever, backache, lower UTI symptoms

30. Copyright © 2015 Wolters Kluwer All Rights Reserved Chronic Pyelonephritis Progressive disease involving scarring and deformation of the calyces Recurrent of persistent bacterial infection superimposed on an obstructive process Symptoms similar to acute May have insidious onset Significant cause of CKD

31. Copyright © 2015 Wolters Kluwer All Rights Reserved Bacterial Invasion of the Kidney Ascending infection from the lower urinary tract Through the bloodstream (septicemia, infective endocarditis)

32. Copyright © 2015 Wolters Kluwer All Rights Reserved Chronic Pyelonephritis

33. Copyright © 2015 Wolters Kluwer All Rights Reserved Drug-Related Nephropathies Functional or structural changes in the kidney following exposure to a drug Kidney cells are exposed to high levels of toxic metabolites Mechanisms of nephropathy –Decreasing renal blood flow (diuretics, contrast media, immunosuppressives, NSAIDs, ASA) –Directly damaging tubulointerstitial structures –Producing hypersensitivity reactions (synthetic antibiotics, furosemide, thiazide diuretics) –Obstructing urine flow (sulfonamides, Vit C)

34. Copyright © 2015 Wolters Kluwer All Rights Reserved Drug-Related Nephropathies Tolerance to drugs varies with age, renal function, state of hydration, BP and pH of the urine Elderly patients are high risk for nephrotoxicity

35. Copyright © 2015 Wolters Kluwer All Rights Reserved Obstructive Disorders Hydronephrosis Renal calculi

36. Copyright © 2015 Wolters Kluwer All Rights Reserved Obstructive Renal Disorders Sudden or insidious Partial or complete Unilateral or bilateral Conditions that cause obstruction: congenital anomalies, urinary calculi, pregnancy, BPH, scar tissue, tumors, neurologic disorders) Classified according to site, degree and duration of obstruction

37. Copyright © 2015 Wolters Kluwer All Rights Reserved Consequences of Dilation of the Renal Tubules or Tract Expansion of the kidney with urine (hydronephrosis) –Increased pressure inside the renal capsule –Compartment syndrome compresses blood vessels inside kidney –Renal ischemia Stasis of urine –Risk of infection –Stones

38. Copyright © 2015 Wolters Kluwer All Rights Reserved Question True or false? Hydronephrosis is categorized as a disorder of glomerular function.

39. Copyright © 2015 Wolters Kluwer All Rights Reserved Answer False Rationale: Hydronephrosis is caused by a urinary obstruction, so it is considered an obstructive disorder. The glomerulus is not involved.

40. Copyright © 2015 Wolters Kluwer All Rights Reserved Renal Calculi (Kidney Stones) Saturation theory: Urine is supersaturated with stone components. Matrix theory: Organic materials act as a nidus for stone formation. Inhibitor theory: A deficiency of substances that inhibit stone formation.

41. Copyright © 2015 Wolters Kluwer All Rights Reserved Four Types of Renal Calculi Calcium stones (i.e., oxalate or phosphate) Magnesium ammonium phosphate stones Uric acid stones Cystine stones

42. Copyright © 2015 Wolters Kluwer All Rights Reserved Renal Calculi (cont.)

43. Copyright © 2015 Wolters Kluwer All Rights Reserved Clinical Features of Renal Calculi Pain –Renal colic: acute, intermittent and excruciating flank pain (caused by stretching of the ureter) –Non-colicky pain: dull, deep ache in the flank or back (caused by distension of the renal calyces or pelvis) Skin cool and clammy Nausea and vomiting Diagnosis: urinalysis, US, IVP, non-contrast CT scan Treatment: pain relief, strain urine, analysis of stone prevent recurrence

44. Copyright © 2015 Wolters Kluwer All Rights Reserved Malignant Kidney Tumors Embryonic kidney tumors –Wilms tumor (occurs in childhood) –Also known as nephroblastoma –Can be unilateral or bilateral –Sharply demarcated, encapsulated mass which usually presents as a protruding abdominal mass –Treated with surgery, chemotherapy –Long term survival rates 70-96%

45. Copyright © 2015 Wolters Kluwer All Rights Reserved Malignant Kidney Tumors Renal cell carcinoma –Usually occurs in adults (incidence peaks between 55 and 84 yrs) –Contributing factors: obesity, occupational exposure to petroleum products, heavy metals, asbestos –Presenting features include: hematuria, flank pain, presence of palpable flank mass –Metastasizes to lung and bone –Diagnosis: CT scan, US –Treatment: surgery –Prognosis: 5 year survival rate is 90%

46. Copyright © 2015 Wolters Kluwer All Rights Reserved Wilms Tumor of the Kidney

47. Copyright © 2015 Wolters Kluwer All Rights Reserved Renal Cell Carcinoma of the Kidney