Chronic kidney disease (CKD) Cases

1. Chronic kidney disease (CKD) Cases Dr. Mohamed Balaha

2. 1. M.R. is a 32-year-old, Native American woman (weight, 63kg) with a 15-year history of type 1 diabetes mellitus. She presents to the diabetes clinic with a 1-week history of nausea, vomiting, and general malaise. She has been noncompliant with regular appointments and her blood glucose has generally remained >200 mg/dL on prior evaluations, with a hemoglobin A1C of 9.1% (goal, < 7%) 2 months ago. M.R. has been treated for peptic ulcer disease for the past 6 months. The workup reveals the following pertinent laboratory values: serum sodium (Na),143 mEq/L (normal, 135–147 mEq/L); potassium (K), 5.3 mEq/L (normal, 3.5–5.0 mEq/L); chloride (Cl), 106 mEq/L (normal, 95–105 mEq/L); HCO3 content, 18 mEq/L (normal, 22–28 mEq/L); SrCr, 2.9 mg/dL (normal, 0.6–1.2 mg/dL); BUN, 63 mg/dL (normal, 8–18 mg/dL); and random blood glucose,

3. 220 mg/dL (normal, 140 mg/dL). Physical examination revealed a BP of 155/102 mmHg, mild pulmonary congestion, and 2+ pedal edema. Additional laboratory studies show serum phosphate, 7.6 mg/dL (goal,3.5–4.6 mg/dL); calcium (Ca), 8.8 mg/dL (goal, 8.4–9.5 mg/dL); magnesium (Mg), 2.8 mEq/L (normal, 1.6–2.4 mEq/L); and uric acid, 8.8 mg/dL (normal, 2.0–7.0 mg/dL). Hematologic studies show hematocrit (Hct), 26% (normal, 36%–46%); hemoglobin (Hgb), 8.7 g/dL (normal, 12–16 mg/dL); and white blood cell (WBC) count, 9,600/mm3 (normal, 3,200–9,800/mm3). Red blood cell (RBC) indices are normal. Platelet count is 175,000/mm3(normal, 150,000–400,000/mm3). M.R.’s reticulocyte count is 2.0% (normal, 0.1%–2.4%). Her urinalysis (UA) showed 4+ proteinuria, later quantified as a urinary albumin of 700 mg/24hrs (normal, < 30 mg/day).

4. A- What subjective and objective data in M.R. are consistent with a diagnosis of advanced kidney disease? • Subjective: • Nausea, vomiting, and malaise may be a consequence of the accumulation of uremic toxins. Also she was noncompliant with regular appointments and • her blood glucose • Objective: • M.R.’s abnormal values for Sr Cr, BUN, serum potassium, magnesium, phosphate, uric acid, HCO3 content, hemoglobin, and hematocrit are all consistent with kidney disease and its associated complications. • - Proteinuria. • Metabolic acidosis • Anemia. • Also, Physical examination revealed a BP of 155/102 mmHg, mild pulmonary congestion, and 2+ pedal edema and type 1 diabetes mellitus.

5. B. What is the cause of M.R.’s advanced kidney disease? • - Caused by diabetic nephropathy • Diabetic nephropathy rarely develops within the first 10 years after onset of type 1 diabetes. The annual incidence is greatest after approximately 20 years’ duration of diabetes. • Diabetic nephropathy is a microvascular complication of diabetes resulting in albuminuria.

6. C. What is the significance of M.R.’s albuminuria? • - Albuminuria, the earliest sign of kidney involvement in patients with diabetes • mellitus, correlates with the rate of progression of kidney disease • - The presence of albuminuria indicates irreversible kidney damage. • - eGFR begins to decline once proteinuria is established. • - Annual testing for the presence of microalbuminuria is indicated in diabetic patients

7. D. How should M.R.’s kidney disease be managed? • - The three main risk factors for the progression of incipient nephropathy to clinical diabetic nephropathy are poor glycemic control, systemic hypertension, and high dietary protein intake (>1.5 g/kg/day). • - The primary goals are to delay the need for dialysis therapy as long • as possible and to manage complications by: • A- Intensive Glucose Control: • - Strict glycemic control is clearly indicated to reduce proteinuria and to slow the rate of decline in eGFR. • - The goal of the intensive regimen is to maintain fasting blood glucose concentrations between 70 and 120 mg/dL, with postprandial blood glucose concentrations <180 mg/dL.

8. B- Antihypertensive Therapy: • -Systemic hypertension usually occurs with the development of microalbuminuria in patients with type 1 diabetes and is present in about one-third of patients at the time of diagnosis of type 2 diabetes. • -The primary goal in M.R. is to delay development of ESRD and to reduce the risk of cardiovascular complications and death. • A goal BP for M.R., based on the fact that she has type 1 diabetes and kidney disease, is a BP <130/80 mmHg. • C- Dietary Protein Restriction: • - High protein consumption accelerates the progression of diabetic nephropathy SO restrict protein intake to 0.6 to 0.8 g/kg/day and maintaining an iso caloric diet.

9. E. M.R. has a serum potassium concentration of 5.3 mEq/L. Describe the mechanisms by which potassium imbalance occurs in patients such as M.R. who have progressive CKD? - Hyperkalemia can result from a combination of factors, including diminished renal potassium excretion, redistribution of potassium into the extracellular fluid owing to metabolic acidosis, and excessive potassium intake. NB: Potassium-sparing diuretics, such as spironolactone, triamterene, and amiloride, should be avoided in patients with severe CKD because they decrease tubular secretion of potassium.

10. F. Assess M.R.’s acid-base status. • M.R.’s low blood HCO3 content and high chloride concentration are consistent with metabolic acidosis.

11. G. What other electrolyte and metabolic disturbances are exhibited by M.R.? • - Hypermagnesemia, Hyperphosphatemia and Hyperuricemia due to their diminished urinary excretion by the kidney. • Hypermagnesemia  nausea, vomiting, lethargy, confusion, and diminished tendon reflexes, WHEREAS severe hypermagnesemia may depress cardiac conduction. • - The risk of hypermagnesemia can be reduced : • by avoiding magnesium-containing antacids and laxatives • and by use of magnesium-free dialysate in patients with stage 5 CKD requiring dialysis.

12. H. What findings in M.R. are consistent with the diagnosis of anemia of CKD, and what is the etiology of this disorder? M.R.’s hemoglobin of 8.7 g/dL and hematocrit of 26% are lower than the normal range for premenopausal females (hemoglobin, 12–16 g/dL; hematocrit, 36%–46%) indicating that she has anemia. - Etiology  decreased production of erythropoietin (EPO) hormone, - EPO, Is a glycoprotein that stimulates red blood cell production in the bone marrow and is released in response to hypoxia.

13. 2- H.B. is a 65-year-old white man with stage 5 CKD who has just started chronic hemodialysis (HD). He comes in today for his third HD session (dialysis scheduled three times per week, 4-hour duration). He has a history of hypertension, which has been poorly controlled over the past 4 months (BP ranges 150–190/85–105 mmHg. His pertinent medical history includes hypertension for the past 14 years. H.B.’s current medications include metoprolol 50 mg BID, furosemide 80 mg BID, calcium carbonate 500 mg TID with meals, and Nephrocaps 1 PO QD. H.B.’s most recent predialysis BP was 175/98 mmHg, and his postdialysis BP was 158/90 mmHg. A recent ECG showed evidence of LVH. What conditions evident in H.B. put him at increased risk of cardiovascular complications and mortality? H.B. has uncontrolled hypertension that is not being adequately managed with his current drug therapy or hemodialysis.

14. 3- D.B. is a 42-year-old white woman who has a 24-year history of type 1 diabetes mellitus with complications of diabetic nephropathy, retinopathy, and neuropathy. She has hypothyroidism and was diagnosed with stage 5 CKD 4 years ago. She started HD three times weekly at that time. Her current medications include levothyroxine, metoclopramide, insulin aspart with meals, insulin glargine,, EPO and Nephrocaps. At a recent clinic visit, findings on physical examination included a BP of 128/84 mmHg, bone pain especially at hip and below the knees. Her laboratory values were normal except BUN, 45 mg/dL (normal,8–18 mg/dL); SrCr, 8.9 mg/dL (normal, 0.6–1.2 mg/dL), Hgb,10 g/dL (goal, >11 g/dL); Ca, 8 mg/dL (normal, 8.4- 9.5mg/dL); phosphate, 6.8 mg/dL (normal, 2.5–5.0 mg/dL); intact parathyroid hormone (iPTH), 450 pg/mL (normal, 5–65 pg/mL). A- What is the mechanism of D.B.’s bone pain?

15. Mechanism In CKD there are - Hyperphosphatemia, hypocalcemia  hyperparathyroidism. Also, decreased production of active vitamin D, and resistance to vitamin D therapy lead to more hypocalcemia  hyperparathyroidism Hyperparathyroidism  renal osteodystrophy (ROD)  bone pain and predisposed to bone fracture ROD is the term used to describe the skeletal manifestations that occur as kidney function declines. Collectively, ROD refers to specific bone abnormalities that include osteitis fibrosa (most common pattern), osteomalacia (deminerlized bone), osteosclerosis, and osteopenia.

16. B- Does D.B.’s hypothyroidism have any relationship to her CKD? What other endocrine abnormalities are associated with uremia? -the kidney is involved in all aspects of peripheral hormone metabolism. - Patients with CKD include thyroidal and gonadal dysfunction. -T4 is not converted to T3 (the active form of thyroid hormone)  hypothyroidism -In children with kidney disease, growth retardation occurs despite normal or elevated growth hormone.

17. - Altered Glucose and Insulin Metabolism  Pseudo-diabetes. Patients with CKD often exhibit an abnormal response to an oral glucose and have sustained hyperinsulinemia, PTH, and glucagon  all hormone are hyperglycemic except insulin is hypo

18. C- One month before her current clinic visit, D.B. complained of nausea and vomiting of partially digested food. Metoclopramide (Reglan) was begun at that time. Could D.B.’s nausea and vomiting have been caused by her kidney failure? Was the appropriate therapy selected? -Gastrointestinal abnormalities are extremely common in patients with CKD caused by uremia . -Metoclopramide is prokinetic recommended to relieve these Symptoms. - But, dialysis is the preferred therapy .

19. D- During her clinic visit, D.B. reports that her bowel movements have become black and tarry in appearance. A rectal examination reveals guaiac-positive stools. Is GI bleeding related to kidney failure? - D.B. should be evaluated for peptic ulcer disease and lower GI bleeding. - Uremic patients are at risk for bleeding from mucosal surfaces such as the stomach.

20. 5- S.H., a 64-year-old, 72-kg, black man, went to his primary care physician because of weakness, nausea, lethargy, decreased exercise tolerance, and general malaise that has developed over the past few weeks. S.H. had not been seen by a physician for >10 years. His medical history was unremarkable, except he recalls being told approximately 5 years ago that he had borderline hypertension. He was taking no medications. The physician’s examination revealed a BP of 168/92 mmHg, and funduscopic examination showed grade III hypertensive changes. On neurologic examination, S.H. was slightly confused, appeared somnolent, and had diminished sensation to pinprick in both lower extremities. Examination of the skin showed pallor and excoriations across the abdomen, legs, and arms.

21. Pertinent laboratory values were as follows: Hct, 20% (normal, 39%–49%); Hgb, 6.7 g/dL (normal, 13–16 g/dL); K, 5.8 mEq/L (normal, 3.5–5.0 mEq/L); Cl, 109 mEq/L (normal, 95–105 mEq/L); CO2 content, 16 mEq/L (normal, 22–28 mEq/L); random blood glucose, BUN, 199 mg/dL (normal, 8–18 mg/dL); SrCr, 19.8 mg/dL (normal, 0.6–1.2 mg/dL); Ca, 8.5 mg/dL (normal, 8.8–10.4 mg/dL); phosphate, 11.1 mg/dL (normal, 2.5– 5.0 mg/dL); intact PTH, 830 pg/mL (normal, 5–65 pg/mL); uric acid, 11.9 mg/dL (normal, 2.0–7.0 mg/dL); and albumin, 3.0 g/dL (normal, 4.0–6.0 g/dL). Renal ultrasonography revealed no obstruction and small kidneys bilaterally. Subsequent kidney biopsy showed chronic glomerular scarring. S.H. was diagnosed with stage 5 CKD, likely caused by chronic, untreated hypertension.

22. A- What is the likely explanation for S.H.’s altered mental status? B- Why does S.H. have excoriations on his skin? Due to uremic pruritus Uremic encephalopathy  Symptoms generally occur when the eGFR is <10% of normal. S.H.’s altered neurologic function is most likely caused by uremia. CAUSES: • Uremic toxin • Increase calcium entrance to CNS cell and neurons