1. 28-Year-Old Man With Crohn Disease and Hematuria
By Prof. Dr. Fawzy Megahed
Ass. Lec. Mahmoud Negm

2. 28-year-old man presented with a 3-month history of mild abdominal pain.

3. His medical history was notable for Crohn disease diagnosed in 1994, complicated by ileocolonic resection (20 cm of ileum and 15 cm of the right colon removed) in 2001.

4. He had been taking mesalamine for 2 years, and although the prednisone dose was increased over the previous 3 months because of recurrent abdominal pain, it produced minimal relief.

5. Computed tomography (CT) revealed fistulizing distal ileal Crohn disease with abscess formation.

6. The patient was hospitalized; ertapenem and vancomycin were initiated, and 2 trials of CT guided abscess drainage were attempted but failed.

7. Twelve days after admission, the patient underwent laparotomy for abscess drainage without any surgical complications.

8. On postoperative day 1, his vital signs deteriorated, with a temperature of 39.3C, respiratory rate of 30 breaths/min, heart rate of 108 beats/min, and blood pressure of 130/80 mm Hg.

9. Pertinent findings on examination included mild respiratory distress and rapid heart rate but regular rhythm and no murmurs.

10. His skin was warm to touch, and no rashes or edema were noted on examination

11. A right lower quadrant drain was in place with minimal blood-tinged drainage.

12. Evaluation included chest CT with contrast medium, which ruled out pulmonary embolism, and blood cultures were obtained.

13. Intravenous ketorolac, 30 mg every 6 hours, was initiated for fever and postoperative pain management.

14. Blood culture results Remained negative after 48 hours, and the vancomycin and ertapenem regimen was continued.

15. On postoperative day 3, laboratory testing yielded the following notable findings (reference ranges provided parenthetically):
hemoglobin, 7.1 g/dL( g/dL);
white blood cells (WBCs), /L ( /L) with 13.8% neutrophils;

16. sodium, 136 mmol/L (135-145mmol/L);
potassium, 3.9 mmol/L ( mmol/L);
serum urea nitrogen, 12 mg/dL(8-24 mg/dL); and creatinine, 1.6 mg/dL ( mg/dL).

17. b. Small vessel vasculitis c. Medullary sponge kidney
1. In patients with Crohn disease, which one of the following is the most commonly associated renal finding?
a. Renal cystic disease
b. Small vessel vasculitis
c. Medullary sponge kidney
d. Nephrolithiasis
e. Diabetic nephropathy

18. Patients with Crohn disease are at considerable risk for multiple lower genitourinary tract and renal parenchymal and interstitial diseases.

19. Renal cystic disease encompasses a wide spectrum of both genetic and acquired forms of renal cysts and has not been associated with inflammatory bowel disease (IBD).

20. Small vessel vasculitis may be associated with antineutrophil cytoplasmic antibodies and manifest as microscopic polyangiitis, granulomatous polyangiitis, or Churg-Strauss syndrome.

21. There have been case reports of antineutrophil cytoplasmic antibodies associated vasculitis in patients with IBD, but this association is rare.

22. Medullary sponge kidney is a congenital abnormality of the collecting tubules in the medullary region causing cystic Dilatation.

23. Medullary sponge kidney has a benign course but is associated with hematuria, nephrolithiasis, and recurrent urinary tract infections. An association with IBD has not been reported.

24. Nephrolithiasis is the most commonly associated renal disease in patients with IBD.

25. Patients with IBD have a 12% to 28% incidence of nephrolithiasis compared with 5% in the general population.

26. Nephrolithiasis tends to be more common in patients with Crohn disease and a history of ileocolonic disease, as in this patient.

27. Diabetic nephropathy has been reported in association with prolonged corticosteroid use in patients with IBD who have development of diabetes, but it does not have a unique association with IBD itself.

28. This patient had no history of chronic kidney disease, proteinuria, hematuria, or acute kidney injury (AKI), and his baseline creatinine concentration ranged between 0.8 g/dL and 1.0 g/dL before the current admission.

29. He had never passed a kidney stone
He had never passed a kidney stone. Abdominal imaging studies performed a few years before admission revealed no renal abnormalities.

30. During the current hospitalization, AKI developed and the creatinine level increased to 1.6 g/dL within 48 hours and peaked at 2.1 g/dL.

31. Urinary output declined to 500 mL in 24 hours the day preceding the increase in creatinine.

32. 2. Which one of the following is the most appropriate next step in the management of this patient’s AKI?
a. Discontinue ertapenem and vancomycin
b. Discontinue ketorolac
c. Initiate N-acetylcysteine
d. Obtain vancomycin trough level
e. Repeat electrolyte panel

33. For several nephrotoxic drugs, administration can be suspended, the pattern of administration changed, or another less toxic or nontoxic drug used instead.

34. However, this strategy cannot be used for all potential nephrotoxic medications. Because the patient meets the criteria for severe sepsis, discontinuing antibiotics may jeopardize his clinical status.

35. Evaluation for antibiotic-induced nephrotoxicity must be pursued before discontinuation.

36. The nephrotoxicity of nonsteroidal anti-inflammatory drugs is mostly attributable to inhibition of renal prostaglandin synthesis.

37. They disrupt the compensatory vasodilation response of renal prostaglandins to vasoconstrictor hormones released in the context of sepsis.

38. These aberrations in renal hemodynamics result in decreased cortical blood flow, decreased glomerular filtration rate, and acute deterioration of renal function.

39. They can also induce acute interstitial nephritis (AIN).

40. Because the patient has had development of AKI and there are other less nephrotoxic medications for pain control available, the most reasonable next step in management is to discontinue ketorolac.

41. N-acetylcysteine may reduce the nephrotoxicity of contrast media through antioxidant and vasodilatory effects when given before administration of contrast but not after the onset of AKI.

42. Its use is still controversial for prevention of contrast-induced AKI.

43. Determining vancomycin trough levels and repeating the electrolyte panel will be helpful to guide next steps, but the most important immediate next step is discontinuation of ketorolac.

44. Ketorlac was discontinued.

45. Further abdominal imaging revealed a fluid collection extending from the right subdiaphragmatic region to the right lower quadrant that was concerning for persistent abscess vs bowel leak as the likely cause for the persistent systemic inflammatory response syndrome.

46. The vancomycin level was monitored and noted to be elevated at 30
The vancomycin level was monitored and noted to be elevated at 30.1 mg/mL (<15 mg/mL).

47. Vancomycin was withheld because of the supratherapeutic levels, and the ertapenem dose was adjusted for renal impairment.

48. Nephrology consultation was requested.

49. 3. Which one of the following is the best test for evaluation of this patient’s AKI?
a. Urinalysis
b. Urinary eosinophil measurement
c. Complement level determination
d. Kidney ultrasonography
e. Measurement of the fractional excretion of sodium (FENa)

50. Urinalysis is the most important step in the evaluation of AKI.

51. The urinalysis includes 2 components, an analysis for proteinuria, leukocyte esterase, glucosuria, bilirubin, and urinary pH and microscopic examination of the urinary sediment, which evaluates for cells, crystals, and casts.

52. Quantification of tubular cells and casts correlates with biomarkers and severity of AKI.

53. Assessment for red blood cells (RBCs), WBCs, and various tubular cells and casts will guide the next steps in evaluation and diagnostic work-up.

54. In clinical practice, urinary eosinophils are often measured to help guide the clinician in determining whether AIN may be the cause of AKI, and based on clinical impressions from nephrologists, sensitivities and specificities for urinary eosinophils have ranged from 40% to 91% and 52% to 95%, respectively.

55. Recent work evaluating the diagnostic utility of urinary eosinophil measurement compared with kidney biopsy, the criterion standard for diagnosis of AIN,

56. found that the presence of urinary eosinophils was not specific for AIN and may occur in many renal disease processes; thus, it may not be useful to differentiate AIN from acute tubular necrosis.

57. Complement levels may be helpful when an immune deposit glomerulonephritis is suspected, but its use should be based on clinical suspicion in conjunction with the presence of RBCs on urinalysis.

58. Kidney ultrasonography is useful to evaluate for the presence of hydronephrosis and kidney stones; however, it should not be the first step in AKI evaluation.

59. The FENa is commonly used to differentiate prerenal vs intrarenal causes of AKI.

60. However, the FENa has only been found to reflect a sodium-avid state or prerenal state in oliguric cases of AKI.

61. Moreover, in early phases of AKI, both intrarenal and extrarenal causes of AKI have been associated with low FENa values resembling those in the prerenal state.

62. The cause of AKI should be based on the global presentation including history, clinical examination, urinalysis, and response to volume resuscitation.

63. Urinalysis revealed granular and hyaline casts, 4 to 10 WBCs per high-power field, and more than 180 RBCs per high-power field.

64. The protein to creatinine ratio and albumin levels were both normal.

65. Gram stain with urine culture yielded negative results.

66. On the basis of the clinical scenario and evidence of granular casts on urinalysis, the cause of AKI in this patient was likely multifactorial due to acute tubular necrosis from several risk factors:
severe sepsis,
nonsteroidal anti-inflammatory
drug use,
recent contrast media exposure.

67. The degree of hematuria noted was concerning for a secondary process.

68. b. Bladder malignant neoplasm c. AIN d. IgA nephropathy
4. On the basis of this patient’s clinical presentation, which one of the following is the most likely explanation for the hematuria?
a. Nephrolithiasis
b. Bladder malignant neoplasm
c. AIN
d. IgA nephropathy
e. Postinfectious glomerulonephritis

69. Nephrolithiasis can be asymptomatic and can cause marked hematuria in the absence of proteinuria.

70. This patient has several risk factors for nephrolithiasis including Crohn disease, history of ileocolonic involvement, and ileal resection.

71. Considering the patient’s young age and no smoking history, a bladder malignant neoplasm is less likely to explain this degree of hematuria.

72. Although both RBCs and WBCs can be present in AIN,WBCs are usually present in greater proportion than RBCs.

73. IgA nephropathy usually manifests as microscopic hematuria in association with proteinuria and often presents at the onset of IBD or during a relapse.

74. Postinfectious glomerulonephritis is an immunologic response of the kidney that occurs after a nonrenal infection, often with streptococci, and is associated with low complement levels.

75. Proteinuria is an important hallmark of this disease process.

76. The presence of RBCs on urinalysis prompted measurements of total complement and C3 and C4 levels.

77. The results were normal, which in conjunction with the absence of any proteinuria makes the diagnosis of postinfectious glomerulonephritis less likely.

78. A review of the patient’s abdominal contrast CT on admission revealed multiple kidney stones in a pattern consistent with medullary nephrocalcinosis, likely explaining the hematuria.

79. The patient’s renal function recovered to baseline within 4 days after the creatinine concentration peaked.

80. He underwent exploratory laparotomy with ileocolonic resection and ileostomy for an anastomotic leak.

81. The patient recovered and was dismissed on the 23rd day of hospitalization.

82. At follow-up 2 months after dismissal, the patient’s creatinine level remained stable.

83. Urinalysis continued to show hematuria and no proteinuria or microalbuminuria, consistent with his underlying medullary nephrocalcinosis.

84. He underwent a 24-hour urinary metabolic evaluation, which yielded 2
He underwent a 24-hour urinary metabolic evaluation, which yielded 2.9 L of urine, normal urinary sodium and calcium levels, low urinary pH (5.4), hypocitraturia, hypomagnesuria, hyperuricosuria, and increased risk for precipitation of calcium oxalate and uric acid crystals.

85. d. Hydrochlorothiazide e. Calcium carbonate
5. On the basis of the 24-hour urinary metabolic evaluation, which one of the following is the most appropriate treatment?
a. Penicillamine
b. Sodium bicarbonate
c. Potassium citrate
d. Hydrochlorothiazide
e. Calcium carbonate

86. This patient has several urinary metabolic risk factors for nephrolithiasis.

87. In addition to careful adherence to high-fluid, low-sodium, low-purine dietary restriction, medical therapy is warranted to decrease the likelihood of future stone formation.

88. Penicillamine is a chelating agent used for the treatment of cystine nephrolithiasis.

89. It forms penicillamine-cysteine disulfide bonds that are easily excreted compared with cysteine-cysteine bonds.

90. There is no role for the use of penicillamine in this patient.

91. Sodium bicarbonate therapy is helpful in patients with evidence of non-anion gap metabolic acidosis, which is often present in patients with chronic diarrhea.

92. This patient does not have evidence of acidemia, and therefore, treatment with sodium bicarbonate is not warranted at this juncture.

93. Potassium citrate is the mainstay of therapy for patients with hypocitraturia and uric acid crystals.

94. Citrate inhibits stone formation and alkalinizes the urine, which increases uric acid crystal solubility and decreases uric acid stone formation.

95. Thiazide like diuretics are useful in patients with hypercalciuria and calcium oxalate stones.

96. This patient has a normal urinary calcium level.

97. Calcium carbonate is often needed for supplementation in patients with low urinary calcium and high urinary oxalate levels, as can be seen in patients with enteric hyperoxaluria.

98. However, this patient has normal urinary calcium and oxalate levels, and therefore, calcium supplementation is not helpful.

99. The patient was encouraged to continue with high fluid intake and a low-sodium diet and was educated about a low-fat, low-purine diet.

100. Potassium citrate tablets were prescribed.

101. DISCUSSION

102. Crohn disease and ulcerative colitis are 2 distinct types of IBD and represent a state of chronic T-celle mediated inflammation that is heavily influenced by genetic predisposition and environmental and lifestyle factors.

103. Up to 23% of patients with IBD will experience lower genitourinary tract and/or kidney involvement, namely in the form of fistulizing disease, interstitial renal disease, and nephrolithiasis.

104. IgA nephropathy has been reported as one of the most common histopathologic findings on kidney biopsies of patients with IBD and is significantly more frequent in these patients than in those without IBD(24%vs8%;P<.01).

105. Several other intra- renal causes of kidney disease have been reported in IBD
AA (previously called secondary) amyloidosis, which has been linked to chronic inflammation;
interstitial nephritis, which has been associated with salicylate therapy as an idiosyncratic drug reaction (necessitating regular monitoring of renal function); and in some reports as a possible direct complication of IBD independent of treatment.

106. Nephrolithiasis in IBD may be asymptomatic, complicated by ureteral obstruction and hydronephrosis, or associated with crystal deposition in renal parenchyma leading to interstitial inflammation and fibrosis.

107. Patients with IBD have a 12% to 28% incidence of nephrolithiasis compared with 5% in the general population.

108. Patients with Crohn disease and ileocolonic involvement are more likely to have development of nephrolithiasis than patients with ulcerative colitis or colonic or ileal disease.

109. Two types of nephrolithiasis predominate in IBD:
Calcium oxalate
Uric acid stones.

110. There are dietary, metabolic, and genetic risk factors that predispose to calcium oxalate stones including hypercalciuria, hyperoxaluria, hypocitraturia, and strong family history.

111. Specific to gastrointestinal disorders, patients with jejunoileal bypass for obesity and pancreatic insufficiency are at highest risk.

112. First, in patients with a diseased or resected ileum, there is decreased bile acid absorption, which consequently leads to fat malabsorption.

113. Calcium is bound by the intestinal fat through the process of saponification, so there is less calcium available to bind to oxalate.

114. Second, deconjugated bile salts have toxic effects on the colonic mucosa that may directly factors.

115. Computed tomography with a stone protocol helps differentiate calcium- from noncalcium-based stones and provides insight into whether stone burden necessitates urological intervention.

116. Review of previous imaging studies will help determine if stones are metabolically active.

117. Urinary metabolic evaluation for sodium, calcium, oxalate, magnesium, and uric acid will help individualize the management approach to minimize future stone formation.

118. For patients with calcium oxalate stones, the focus of treatment is to increase the luminal calcium concentration with calciumcarbonate supplementation and dietary restriction of fat and oxalate.

119. For those with uric acid stones, the key treatment is alkalinization of the urine with potassium citrate, and if hyperuricosuria is present, allopurinol and a purine-restricted diet are recommended.

120. Close follow-up is essential to monitor nephrolithiasis risk factors, adjust treatment, and assess for changes in stone type over time.

121. Patients with IBD and risk factors for nephrolithiasis benefit from regular urinalysis to assess for hematuria.

122. Patients with metabolically active or symptomatic kidney stone disease will benefit from tailored treatment to decrease further stone formation and risk for associated complications.

123. Thank you