Chronic kidney disease (CKD) Cases

Mohammad Ruhal AinR Ph, PGDPRA, M Pharm

(Clin. Pharm)Department of Clinical Pharmacy

DIABETIC NEPHROPATHY

Case 1

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 6months. 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); CO2 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, 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, 7.6mg/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, 130,000–400,000/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) .

What subjective and objective data in M.R. are consistent with a diagnosis of advanced kidney disease?

Subjective:M.R.’s abnormal values for Sr Cr, BUN, serum potassium, magnesium, phosphate, uric acid, CO2 content, hemoglobin, and hematocrit are all consistent with kidney disease and its associated complications.

-Proteinuria. -Metabolic acidosis results from impaired synthesis of ammonia by the kidney. -Anemia associated with CKD is caused primarily by decreased erythropoietin

production by the kidneys .,-Nausea, vomiting, and malaise may be a consequence of the accumulation of uremic

toxins.

objectivePhysical examination revealed a BP of 155/102 mmHg, mild pulmonary congestion,

and 2+ pedal edema and type 1 diabetes mellitus.

2 .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 .

-The exact mechanisms diabetic nephropathy are not clearly defined; however, several RISK factors for the development and progression of kidney damage .

-These include: -elevated BP ,plasma glucose, glycosylated hemoglobin, and cholesterol; smoking;

advanced age ;male gender; and potentially, high protein intake.Pathogenesis:

1-Insulin deficiency. 2-Increased ketone bodies.

3 -Advanced glycosylation end products (AGE).

3 .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

4 .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 longas 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.

-the intensive insulin regimen reduced the overall risk of microalbuminuria (defined as urine albumin ≥40 mg/24 hours) and albuminuria(defined as urine albumin ≥300 mg/24 hours)

-insulin or an oral sulfonylurea reduced microvascular complications

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.

•ACE + ARB=take care of adverse effect ??30% SrCr , Hyperkalemia.•Calcium Channel Blocker (,verapamil, diltaizem ) •Nondihydropyridine calcium channel blocker (e.g., diltiazem, verapamil) may be beneficial alone or in combination with Dirutics (loop ).•Diuretic (loop = furosemide) , ( thiazide).• Thiazied not used when eGFR <30mL/minute/1.73m2

•Spironolactone contraindicated in patient with Hyperkalemia•Dilators.

C- Dietary Protein Restriction:

-High protein consumption accelerates the progression of diabetic nephropathy, presumably because of increased glomerular hyperfiltration and intraglomerular pressure.

-Restricting protein intake to 0.6 to 0.8 g/kg/day and maintaining an iso caloric diet .

5 .Assess M.R.’s sodium and water balance. What interventions may be used to address this problem?

-These mechanisms enable patients to maintain relatively normal sodium and water homeostasis.

- As illustrated in M.R., patients in the latter stages of CKD commonly retain sodium and water .

-This is supported by M.R.’s elevated BP, 2+pedal edema, and mild pulmonary congestion.

-glomerular and tubular adaptive processes develop, such as an increase in the fractional excretion of sodium(FENa) .

-normal serum sodium concentration indicates, this value is of little use in establishing the diagnosis of total body sodium and fluid excessbecause retention of sodium and water usually occurs in an isotonic fashion.

-Expansion of blood volume, if not controlled, can cause peripheral edema, heart failure, and pulmonary edema.

-

management of sodium and water retention is essentiaL by:- sodium restriction (∼2 to 4 g/day)

- and fluid restriction (∼2 L/day) . -Diuretic therapy ,

usually with loop diuretics (e.g., furosemide, bumetanide,) is often required. Combination therapy with two different types of diuretics (i.e., loop and thiazide) may be successful in patients resistant to a single agent;

However, limitations in efficacy of diuretics exist under certain conditions (e.g., a reduced eGFR and hypoalbuminemia) ,

-As kidney failure progresses, manifestations of excess fluid accumulation develop that are resistant to more conventional interventions, and dialysis will be required to control volume status.

6 .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.A variety of factors affect this distal secretion of potassium.

-Additional factors that alter potassium homeostasis include metabolic or respiratory acidosis. Acidotic conditions can cause a redistribution of intracellular potassium to the extracellular fluid.

-Potassium-sparing diuretics, such as spironolactone (Aldactone), triamterene (Dyrenium), and amiloride (Midamor), should be avoided in patients with severe CKD because they decrease tubular secretion of potassium.

7 .Is treatment of M.R.’s potassium indicated? How should severe hyperkalemia be managed?

- -M.R. has a mild elevation in potassium to 5.3mEq/L; therefore, no specific treatment is required.We have A Specific treatment and NON-Specific treatment.

-Goals of therapy include prevention of adverse events related to excessive potassium and reduction of serum potassium concentrations to a relatively normal range (4.5–

Treatment of hyperkalemia depends on the serum concentration of potassium as well as the presence or absence of symptoms and electrocardiographic (ECG) changes.

-Early ECG changes

-Manifestations of hyperkalemia include weakness, confusion, and muscular or respiratory paralysis.

-Ventricular arrhythmias or cardiac arrest may ensue if no effort to lower5.5 mEq/L.)

--Generally, treatment is unnecessary if the potassium concentration

is<6.5mEq/L:

NON-SPECIFIC:

- -Chronic management involves prevention of hyperkalemia by limiting potassium

-intake and avoiding the use of agents that could elevate potassium levels.

-SPECIFIC:

-Acute management involves reversal of cardiac effects with calcium administration and reduction of serum potassium .

-The latter can be achieved by shifting potassium intracellular with - ---administration of glucose and insulin,

---- β-adrenergic agonists.-----or alkali therapy (if metabolic acidosis is a contributing factor) and

------by removing-potassium using exchange resins or dialysis--.

8 .Assess M.R.’s acid-base status. How should her acid-base disorder be managed?M.R.’s low blood CO2 content and high chloride concentration are consistent with metabolic acidosis.

M.R.’s mild acidosis should be treated with a goal of normalizing the plasma bicarbonate concentration or at least achieving bicarbonate levels near≥22mEq/L.

Treatment includes use of preparations containing:

---sodium bicarbonate ----or sodium citrate, Shohl’s solution and Bicitra.

If a patient such as M.R. is sodium and fluid overloaded,--Polycitra, or potassium citrate, is a possible alternative; however, the

potassium content limits its use in patients with more severe kidney disease .

-Citrate also promotes aluminum absorption and should not be used in patients taking aluminum-containing agents.

9 .What other electrolyte and metabolic disturbances are exhibited by M.R?.

-The mild degree of hypermagnesemia seen inM.R. is a common finding in patients with CKD owing to decreased elimination of magnesium by the kidney.

-M.R.’s hyperphosphatemia is a result of decreased phosphorus elimination by the kidneys (see Question 17 for a more detailed discussion of hyperphosphatemia).

-M.R. also has mild hyperuricemia. Asymptomatic hyperuricemia frequently develops in patients with kidney disease owing to diminished urinary excretion of uric acid.

Higher concentrations of hypermagnesemia can lead to 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.

10 .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 substantially lower than the normal range for premenopausal females (hemoglobin, 12–16 g/dL; hematocrit,

36%–46%) indicating that she has anemia.

-the absence of an elevated reticulocyte count suggests an impaired bone marrow response for her degree of anemia.

-Etiology:

caused by a decreased production of erythropoietin (EPO), )EPO ,(Is a glycoprotein that stimulates red blood cell production in the bone

marrow and is released in response to hypoxia-Approximately 90% of the total EPO is produced in the peritubular cells of the

kidney;the remainder is produced by the liver..

11 .What are the goals of therapy for anemia of CKD in M.R?.

Guidelines recommend a target of ≥11 g/dL for hemoglobin (≥33% for hematocrit) in patients with CKD receiving ESA therapy.

It is at these targets that benefits such as increased survival, exercise capacity, quality of life, cardiac output, cognitive function, and decreased risk of LVH were observed in the CKD population.

Hemoglobin, rather than hematocrits, should be used to evaluate anemia in this population for several reasons .

12 .Describe the options available to treat anemia of CKD and achieve the goals of therapy in M.R.

A-Iron Therapy:-Oral iron is reasonable for M.R .

-Oral iron supplementation with 200 mg/day of elemental iron should be started to address iron deficiency.

-Sodium ferric gluconate and iron sucrose are the most widely used iron products in

the CKD population.

B-Erythropoiesis Stimulating Agent (ESA) Therapy:

Recombinant human EPO is the primary treatment option for patients with anemia of CKD.

C- Folic acid.

CARDIOVASCULAR COMPLICATIONS13 .H.B. is a 65-year-old white man with stage 5 CKD who has just started

chronic 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), and he has experienced shortness of breath and a significant weight gain over the past month. 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 BPwas 175/98 mmHg, and his postdialysis BP was 158/90 mmHg. A recent ECG showed evidence of LVH. Predialysis laboratory values were as follows: serum sodium (Na), 140 mEq/L (normal, 135–147 mEq/L); potassium (K), 5.1mEq/L (normal, 3.5–5.0 mEq/L); chloride (Cl), 101 mEq/L (normal,95–105 mEq/L); CO2 content, 23 mEq/L (normal, 22–28mEq/L); SrCr, 8.8 mg/dL (normal, 0.6–1.2 mg/dL); BUN, 84mg/dL (normal, 8–18 mg/dL); phosphate, 5.2 mg/dL (normal,2.5–5.0 mg/dL); Ca, 8.6 mg/dL (normal, 8.8–10.4 mg/dL); serum albumin, 3.0 g/dL (normal, 4.0–6.0 g/dL); cholesterol (nonfasting), 345 mg/dL (normal,<200 mg/dL); triglycerides, 285 mg/dL(normal,<200 mg/dL); Hct, 27% (normal, 39%–49%); and Hgb,9.0 g/dL (normal, 13–16 g/dL). H.B. has a urine output of 50 mL/day.

*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 .What options are available to treat H.B.’s hypertension considering his other cardiac complications and BP goal?

-Dialysis-Antihypertensive Therapy:

Antihypertensive therapy should be used in conjunction with dialysis therapy in H.B. to target a BP<140/90 mmHg pre-HD and <130/80 mmHg post-HD.

-example of drug : Diuretics , ACE , ARB , Calcium channel blocker , B-blocker

*15. How should H.B.’s lipid abnormalities be treated?-Dietary intervention successfully, Statin-

Reduces triglyceride and cholesterol concentrations.

SECONDARY HYPERPARATHYROIDISM AND RENAL OSTEODYSTROPHY

16 .D.B. is a 42-year-old white woman who has a 24-yearhistory of type 1 diabetes mellitus with complications of diabeticnephropathy, retinopathy, and neuropathy. She has hypothyroidismand was diagnosed with stage 5 CKD 4 years ago. Shestarted HD three times weekly at that time. Her current medicationsinclude levothyroxine 0.1 mg/day, metoclopramide (Reglan)

10 mg TID before meals, insulin aspart 10 U with meals, insulinglargine 25 U QHS, docusate 100 mg QD, OsCal 500 mg PO TIDwith meals, EPO 5,000 U IV twice weekly, iron sucrose 100 mgIV (TIW), paricalcitol 1 mcg IV three times per week (TIW),and Nephrocaps 1 capsule QD. At a recent clinic visit, findingson physical examination included a BP of 128/84 mmHg, diabeticretinopathic changes with laser scars bilaterally, and diminishedsensation bilaterally below the knees. Her laboratory values wereas follows: normal serum electrolytes; a random blood glucose

of 175 mg/dL (normal, 140 mg/dL); 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); WBC count, 6,200/mm3 (normal, 3,200–9,800/mm3); Ca, 8.5 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); total serum protein, 5.0 g/dL (normal, 6.0–8.0 g/dL); serum albumin, 3.1 g/dL (normal, 4.0–6.0 g/dL); and uric acid, 8.9 mg/dL (normal,2.0–7.0 mg/dL).

*Describe the etiology of D.B.’s abnormal bone, calcium, phosphorus, and PTH findings.

EtiologyRenal osteodystrophy (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.

Hyperphosphatemia, hypocalcemia, hyperparathyroidism, decreased production of active vitamin D, and resistance to vitamin D therapy are all frequent problems in CKD that can lead to the secondary complication of ROD.

*17 .What are the goals of therapy for D.B.’s calcium, phosphorus, and PTH abnormalities? What options are available to treat these disorders?

-The management objectives for D.B. are to (a ) Maintain - near normal serum calcium and

phosphorus concentrations,(b ) , prevent secondary hyperparathyroidism and (c ) Restore normal skeletal development without

inducing a dynamic bone Disease .These goals are best achieved with:

-- dietary phosphorus restriction,-- appropriate use of phosphate-binding agents,

-- Vitamin D therapy, calcimimetics, and dialysis.

- OTHER PHOSPHATE BINDERS : Aluminum preparations.

-Vitamin D (CALCITRIOL) .It is thought to decrease PTH messenger RNA(mRNA) resulting in decreased PTH secretion. It also lowers the calcium set point for PTH release in patients with CKD with sHPT.

-Calcimimetics :this agent demonstrated efficacy in lowering PTH concentrations and Ca-P product in patients.

-Parathyroidectomy.

Endocrine Abnormalities Caused by Uremia*18 .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.

-In children with kidney disease, growth retardationoccurs despite normal or elevated growth hormone.

-T4 is not converted to T3 ( PTH)

Altered Glucose and Insulin Metabolism *Other than the obvious effect of D.B.’s diabetes

mellitus on blood glucose, are there any effects of kidney disease itself on glucose metabolism?

-Pseudodiabetes. Specifically, patients with CKD often exhibit an abnormal response to an oral glucose and have sustained hyperinsulinemia .,PTH, and glucagon also may contribute to glucose intolerance.

NOTE: ALL HORMONE IN THE BODY ARE HYPERGLYCEMIC EXCEPT INSULIN IS HYPO

Gastrointestinal Complications*20 .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.

-dialysis is the preferred therapy .

Bleeding*21 .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. D.B.’s hemoglobin and hematocrit are below the target values (11–12 g/dL for hemoglobin, 33% to 36% for hematocrit)TREATMENT:

1-Antiacid2-H2 receptor ( antacid)

3 -Proton-Pump inhibior (omeprazole)

NEUROLOGIC COMPLICATIONS

Chronic Kidney Disease

Case 1S.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; asterixis was present. Examination of the skin showed pallor and excoriations across the abdomen, legs, and arms.

Pertinent laboratory values were as follows: Hct, 20% (normal, 39%–49%); Hgb, 6.7 g/dL (normal, 13–16 g/dL); WBC count, 9,100/mm3 (normal, 3,200–9,800/mm3); serum Na, 135 mEq/L (normal, 135–147 mEq/L); 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, 121 mg/dL (normal, <140 mg/dL); 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.

What is the likely explanation for S.H.’s altered mental status? What treatment, if any, is indicated for his neurologic findings?

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

Treatment :1- Dialysis.2- Correction of his hyperparathyroidism.

Dermatologic Complications

Why does S.H. have excoriations on his skin? What therapy would be useful?

Uremic pruritus

Treatment :1- Dialysis.2- Oral antihistamines (e.g., hydroxyzine).3- Topical emollients or topical steroids.

Case 2C.W., a 34-year-old black woman with a 7-year history of

SLE, presents to the nephrology clinic for follow up of her LN. Pertinent laboratory values are as follows: serum Na, 146 mEq/L (normal, 135–147 mEq/L); K, 4.2 mEq/L (normal, 3.5– 5.0 mEq/L); Cl, 100 mEq/L (normal, 95–105 mEq/L); CO2 content, 25 mEq/L (normal, 22–28 mEq/L); SrCr, 2.0 mg/dL (normal, 0.6–1.2 mg/dL); BUN, 20 mg/dL (normal, 8–18 mg/dL); and WBCcount, 9,600/mm3 (normal, 3,200–9,800/mm3). RBC indices were normal. Platelet count is 175,000/mm3 (normal, 130,000– 400,000/mm3). Her 24-hour urine contained 2.3 g of albumin (normal, <30 mg/day), and her urine analysis shows 12 RBC/highpower field (HPF) (normal, 0–3). Compared with her visit of a week ago, C.W.’s kidney function and urinary indices (proteinuria, hematuria) show substantial worsening of her nephritis. C.W. was hospitalized, and a kidney biopsy showed inflammation of 40% of the glomeruli.

Should C.W.’s LN be treated?

SLE : auto immune disease occurred when the immune system misrecognition it’s own organs.

treatment of LN involves suppression of the immune system with corticosteroids and cytotoxic agents.