Chronic kidney disease case file

Chronic Kidney Disease Case File

Eugene C. Toy MD, Donald Briscoe, MD, FA  AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA  AFP, FACG

Case 21

A 46-year-old woman presents to the clinic for the first time, complaining of decreased urinary output for 5 months with a foamy appearance. She also complains of swelling in both legs and non bloody, non bilious emesis a few times a week. She was diagnosed with diabetes 10 years ago and has been taking insulin for 2 years. She does not check her sugars at home because she does not like to "stick" herself. When asked about her diet she states that she eats the best she can for what she can afford but often has very little appetite. The patient last saw her physician 8 months ago and insulin is her only medication. On examination, the patient is an obese woman. Her temperature is 99°F (37.2°C), her heart rate is 108 beats/min, her blood pressure is 198/105 mm Hg, her respiration is 19 breaths/ min, and her oxygen saturation is 94% on room air. A head, ears, eyes, nose, and throat (HEENT) examination reveals periorbital edema. Her skin is hyperpigmented on both lower extremities. Her heart is tachycardic with an S1, S2, S4 gallop auscultated with no murmur or rub. When palpating the heart's point of maximal impulse (PMI), it is lateral to the left midclavicular line. There are vesicular breath sounds in both lungs throughout. Her neck reveals no jugular venous distension and there are no carotid bruits. Her abdomen is nontender, with no bruits or masses palpated. The lower extremities reveal pitting pretibial edema with a pit recovery time less than 40 seconds. Laboratory studies in your office include a urinalysis showing hyaline casts, 3+ proteinuria, and glucose, but negative for ketones. Her hemoglobin is 10.9 g/dl and her hematocrit is 32% with a mean corpuscular volume (MCV) of 82.3 g/dl.

⯈ What is the most likely diagnosis?

⯈ What is your next diagnostic step?

⯈ What is het next step in therapy?

ANSWER TO CASE 21:

Chronic Kidney Disease

Summary: This is a 46-year-old woman with chronic kidney disease (CKD). She has a history of uncontrolled diabetes and currently has uncontrolled hypertension. She presents with periorbital edema, long-standing lower-extremity edema, an S4 and displaced PMI, and central obesity. The urinalysis shows hyaline casts, 3+ proteinuria and glucose, negative ketones, and hemoglobin 10.9 g/dL with an MCV of 82.3 g/dL.

• Most likely diagnosis: Acute worsening of CKD
• Next diagnostic step: Measurement of serum electrolytes, blood urea nitrogen (BUN), and creatinine; imaging of the kidneys
• Next step in therapy: Further history to identify and remove any offending agents (such as nonsteroidal anti-inflammatory drugs [NSAIDs]), and control of blood pressure and diabetes; may require dialysis if she develops complications such as pulmonary edema, severe hyperkalemia, or anuria

ANALYSIS

Objectives

1. Know the risks for developing CKD.
2. Learn to evaluate for CKD.
3. Be familiar with the management of CKD.
4. Recognize the complications associated with CKD.

Considerations

This 46-year-old patient presents with a concerning symptom of a decrease in urination with a change in the appearance of the urine. The most immediate concern is how often she is urinating and to what degree she is urinating less. A significant reduction requires immediate evaluation of creatinine function and volume status. Volume status is assessed by skin turgor, mucous membranes, specific gravity in the urinalysis, and orthostatic blood pressure, which also measures heart rate in the lying, sitting, and standing positions. A low volume status with an elevated creatinine requires that the patient be given IV fluids to see if there can be any recovery of kidney function. The patient's uncontrolled diabetes and hypertension predispose her to kidney damage. Another common offender is a patient with this history who is taking NSAIDs. This will increase the patient's already high risk of damage.

With CKD, patients are often able to compensate for the metabolic imbalances that occur such as hyper- or hyponatremia, hyperkalemia, elevated uric acid levels, and metabolic acidosis. Patients also experience secondary hyperparathyroidism. Significantly elevated potassium levels require treatment with sodium polystyrene sulfonate (Kayexalate), insulin with glucose, and retention enemas, depending on the degree of elevation. When the patient is no longer compensating, there are symptoms of pulmonary edema, which include shortness of breath, lower-extremity edema, jugular venous distension, and abnormal lung sounds (rales). This patient was compensating and mostly demonstrated the result of a hypoalbuminemic state from the loss of protein in the urine. She had lower-extremity edema with a long pit time that reflected her low albumin state. Her occasional emesis reflects high levels of urea and other toxins. Persistent emesis mandates treatment. Her normocytic anemia was the result of reduced erythropoietin from the kidneys. In this setting, treatment with exogenous erythropoietin improves prognosis for cardiovascular mortality. The hyaline casts reflect the long-standing damage to the kidneys.

Increasing the patient's chance of improved kidney function requires glucose and blood pressure control, removing offenders such as NSAIDs and diuretics (if allowable), maintaining normal volume status (which is difficult with a low albumin state), and adding agents that both treat blood pressure and improve kidney and cardiovascular function such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). CKD itself is a cardiovascular risk factor. Patients are more likely to die from cardiovascular disease than to develop end-stage renal disease (ESRD) requiring dialysis. The patient's gross proteinuria of 3 + reflects her high risk for cardiovascular disease.

Approach To:

Chronic Kidney Disease

DEFINITIONS

CKD: A spectrum of processes associated with abnormal kidney function and progressive decline in glomerular filtration rate (GFR).

ESRD: The irreversible loss of kidney function such that the patient is permanently dependent on renal replacement therapy (dialysis or transplantation). It is also defined as a GFR of less than 15 mL/ min.

CLINICAL APPROACH

Etiologies

CKD is becoming more common in the United States. The most common etiologies are diabetes, hypertension, and glomerulonephritis. Diabetic kidney disease occurs in 30% to 40% of type I diabetics, in 25% of type II diabetics, and in 24% of hypertensive patients. Within the diabetic patient population, 20% to 60% have hypertension. Many patients present at a later stage of CKD and it is then difficult to determine the etiology.

Evaluation

The Kidney Disease Outcomes Quality Initiative (KDOQI) from the National Kidney Foundation (NKF) recommends both a serum creatinine (Cr) to estimate

GFR and random urinalysis for albuminuria in those groups at risk for CKD. The stage of CKD is based on GFR, which can be estimated with a random Cr level calculated with one of two commonly used equations:

Modification of Diet in Renal Disease (MDRD) equation:

GFR (mL/min/1.73 m2) = 186 X (Scr)-1,54 X (age)-0.203 X (0.742, if female) Xx

(1.210, if black)

Cockcroft-Gault equation:

Ccr (mL/min) = ((140 - age] X weight [kg])/(72 X Scr) X (0.85, if female)

(SCr= serum creatinine concentration; Ccr = creatinine clearance)

A normal GFR is between 90 and 120 mL/ min. Stage 1 of CKD correlates with a GFR more than 90 mL/min in the presence of signs of kidney disease, such as proteinuria, hematuria, or abnormal renal structure; stage 2 correlates with a GFR of 60 to 89 mL/min; stage 3 correlates with a GFR of 30 to 59 mL/min; stage 4 correlates with a GFR of 15 to 29 mL/ min; and stage 5 correlates with a GFR less than 15 mL/min or dialysis. The Cockcroft-Gault equation is preferred for older patients and in renal dosing of medications. It is important to note that these equations do not give an accurate calculation of GFR in the setting of an acute change in renal function, such as acute kidney injury. Serial measurements of renal function are recommended for newly diagnosed cases to determine the pace of renal deterioration and whether the disease is truly chronic, as opposed to acute or subacute. A 24-hour urine collection is recommended for persons with extremes of age and weight, malnutrition, skeletal muscle disease, paraplegia or quadriplegia, or a vegetarian diet.

The evaluation in all patients with CKD includes renal imaging (typically with renal ultrasound) and microscopic evaluation of urine. Treatment may be more successful in patients with normal-size kidneys. Small kidneys show irreversible disease. Asymmetry suggests renovascular disease. Evidence of proteinuria or microalbuminuria should be evaluated in all patients with CKD. If the urine dipstick does not reveal gross proteinuria, a sample should be sent to evaluate for microalbumin. A test is positive if there is more than 30 mg of microalbumin per gram Cr. It is recommended in the case of less than 200 mg of protein per gram Cr that the test be repeated yearly. Any patient with more than 200 mg of protein per gram Cr will need diagnostic evaluation and treatment. The protein-to-creatinine ratio in an early-morning random urine sample may be used instead of a 24-hour urine protein excretion.

Underlying causes may be ascertained through clinical presentation, symptomatology, and past medical and family history. Some common laboratory studies include antinuclear antibody (ANA), antiphospholipid antibodies, C3, C4, erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) (looking for lupus nephritis), hepatitis panel and HIV test (looking for infectious etiologies), serum and urine protein electrophoresis (looking for multiple myeloma) for those patients older than age 35, hemoglobin Ale, fasting blood sugar, and analysis of urine sediment. Renal biopsy, if not contraindicated by comorbidities, is indicated in patients with unknown etiology after history and laboratory evaluation, if parenchymal disease is suspected, or if treatment or prognosis will be based on

the biopsy. However biopsy is contraindicated if bilateral small kidneys are seen on imaging, as there is a low likelihood of improving outcome due to the presence of late-stage disease. Common conditions associated with CKD, such as anemia and hyperphosphatemia should be tested for.

Management

Managing CKD includes treatment of reversible causes. Hypovolemia, hypotension, infection leading to sepsis, and drugs that lower the GFR all reduce renal perfusion. History and physical examination allow for this diagnosis, and a trial of fluids may improve kidney function. Drugs such as NSAIDs, aminoglycosides at full strength, and radiographic contrast material can affect kidney function. Urinary tract obstruction, commonly caused by prostate enlargement in elderly men, is a potentially reversible cause.

Nonproteinuric renal disease requires strict blood pressure control. JNC 8 guidelines recommend blood pressure goal of less than 140/90 mm Hg in all patients age 18 or older with CKD. Multiple guidelines recommend blood pressure goal of less than 130/80, especially if there is diabetes or proteinuria. Another goal is the reduction of protein excretion to less than 500 to 1000 mg/ d (or at least 60% of the baseline value). JNC 8 guidelines recommend starting with an ACE inhibitor or an ARB for blood pressure control in patients with CKD, followed by a thiazide diuretic or calcium channel blocker if the blood pressure goal is not achieved. β-Blockers may also be considered as second- or third-line treatment for blood pressure control. Combining both an ACE inhibitor and an ARB is not recommended.

Other treatments may be beneficial in CKD. Dietary protein restrictions of 0.8 to 1.0 mg/kg/ d may be beneficial. Statins are recommended for treatment of hyperlipidemia in most CKD patients not on dialysis. The volume overload associated with CKD responds well to sodium restriction and loop diuretics. This lowers the intraglomerular pressure. Hyperkalemia may be prevented by a low-potassium diet and avoiding drugs such as NSAIDs and, sometimes, ACE inhibitors. Metabolic acidosis may be treated with sodium bicarbonate, with a goal to maintain a concentration of 22 mEq/L. Dietary phosphate restriction may limit the development of secondary hyperparathyroidism in these patients. Vitamin D supplementation has moderate evidence for reduction in all-cause mortality. Patients should also have influenza, pneumococcal vaccinations. Those with high risk of progression should also receive hepatitis B vaccination.

When the GFR is below 25 to 30 mL/min, oral phosphate binders are usually required. Caution is used when treating hyperphosphatemia in stages 3 to 5 CKD. It is suggested that calcium intake not exceed 2000 mg/d, as this may contribute to cardiovascular disease.

Guidelines suggest evaluation of anemia with hemoglobin less than 12 g/ dL in females and 13.5 g/ dL in adult males. This should include evaluation for nonrenal causes of anemia.

Treating patients with CKD with erythropoietin if hemoglobin is less than 10 g/dL to goal less than 12 g/dL in low-risk patients and less than 13 mg/dL in those at risk for stroke and cardiovascular events may reduce symptoms of anemia, show cardiovascular improvement, and possibly decrease mortality. Ultimately, the patient that is going toward ESRD must be identified and adequately prepared for renal replacement therapy. It is recommended that patients with a GFR less than 30 mg/ dL, difficult to control comorbidities, significant proteinuria, or sudden worsening of renal function be referred to a nephrologist for evaluation and preparation for possible dialysis.

CASE CORRELATION

• See also Case 14 (Hematuria).

COMPREHENSION QUESTIONS

21.1 A 56-year-old man with known CKD presents with a 3-day history of shortness of breath and rapid weight gain. On examination, you are able to auscultate an S3, hear crackles at the bases, and see moderate jugular venous distension (JVD). Which of the following is your next step in evaluation?

A. Perform an echocardiogram.

B. Order a chest x-ray.

C. Measure a Cr to calculate GFR.

D. Check for cardiac enzymes.

21.2 A 39-year-old woman with multiple medical problems has been noted to have progressively worsening renal insufficiency. Which of the following measures is most important in the prevention of end-stage renal disease?

A. Tobacco cessation

B. Triglyceride control

C. Glycemic control

D. Weight control

E. Dietary sodium restriction

21.3 A 72-year-old man, with a long history of hypertension, presents to the emergency department (ED) complaining of a 2-day history of emesis and 36 hours of no urination. On examination, the abdomen is firm and tender, and the prostate is enlarged. His serum creatinine level is 3.4 mg/ dL. Which the following is the best next step?

A. Give him IV fluids and see if he begins to make urine.

B. Perform a renal ultrasound in the ED.

C. Maintain tight control of his blood pressure.

D. Place an indwelling Foley catheter.

21.4 A 45-year-old woman with type 2 diabetes presents to the clinic with decreased vision in the left eye for 1 year, 1 + proteinuria, a baseline Cr of 1.6 mg/ dL, an low-density lipoprotein (LDL) of 135 mg/dL, blood pressure of 145/92 mm Hg, and occasional chest pain for the past 2 months. Which of the following is the best medication to start the patient on at this time?

A. ACE inhibitor

B. β-Blocker

C. Oral nitrate

D. Thiazide diuretic

ANSWERS

21.1 B. The patient has CKD with volume overload as evidenced by symptoms and physical examination. A simple first step is to do a chest x-ray to confirm what you already suspect-pulmonary edema. After initiating furosemide (Lasix), the chest x-ray may be repeated to see to what degree the diuresis has improved the overload. Cardiac workup is also indicated but would not be the first test done.

21.2 C. Optimal control of high blood pressure, acidosis, volume depletion, and cholesterol are all important to prevent worsening renal function. Diabetes is a leading cause of end-stage renal disease. Tight glycemic control can prevent the microvascular complications of diabetes such as diabetic nephropathy, though it has not been shown to decrease significantly the occurrence of macrovascular complications of diabetes such as coronary artery disease (CAD) or peripheral vascular disease (PVD). Treating secondary hyperparathyroidism prevents complications such as renal osteodystrophy. The patient's weight does not impact on renal function substantially. Smoking has numerous health risks but does not tend to impact kidney function directly; nevertheless, its effect on cardiovascular system may impact on the kidneys.

21.3 D. The patient has an enlarged prostate that has caused urinary obstruction and potentially reversible renal failure, depending on at which point the obstruction is resolved. Placing the Foley catheter will usually allow for significant reversal of an elevated Cr. Following catheter placement, the urine output needs to be carefully monitored and the Cr repeated later. Another clue is the tense lower abdomen that is caused by a very enlarged bladder. It is especially important to rely on clinical examination skills in elderly patients who have less-than-optimal communication skills as a consequence of dementia or who have a history of stroke when evaluating for a cause.

21.4 A. ACE inhibitors would help in hypertension treatment and to protect renal function in this patient. Both diabetes and CKD are known to be cardiovascular risk equivalents. Other factors, such as uncontrolled blood pressure and cholesterol, add to the patient's high risk, which is why it is so important for all diabetics and CKD patients to improve all modifiable risk factors. The goals become much more stringent when looking at these two groups of patients.

CLINICAL PEARLS

⯈ Small kidneys on imaging usually reflect irreversible disease. Small kidneys should rarely be biopsied, as the result of the biopsy usually will not alter the treatment or prognosis of the condition .

⯈ Calculation of the estimated GFR using the Cockcroft-Gault formula is an important process as, especially in older persons, a seemingly normal serum creatinine could reflect a significant reduction in GFR and could affect dosing of medications.

REFERENCES

Bargman JM, Skorecki K. Chronic kidney disease. In: Kasper D, Fauci A, Hauser S, et al., eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY : McGraw-Hill; 2015. Available at: http:// accessmedicine.mhmedical.com. Accessed May 25, 2015. 

Fowler M. Microvascular and macrovascular complications of diabetes. Clin Diabetes. 2008;26:2. Available at: http://clinical.diabetesjournals.org/ content/26/2/77.full.pdf+html. Accessed May 2009. 

James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the eighth Joint National Committee (JNC 8).JAMA. 2014;311(5):507-520. 

Kidney Disease Improving Global Outcomes clinical practice guideline for lipid management in chronic kidney disease: 2013 update. Kidney Int Suppl. 2013;3:263-264. 

National Kidney Foundation. NKF-KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am] Kidney Dis. 2006;47(suppl 3):S26. 

National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis. 2012;60(5):850-886. 

Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 June 6;358(24):2560-72. Available at: http:// dx.doi.org/ 10.1056/NEJMoa0802987. Accessed June 2009. 

RiveraJA, O'Hare AM, Harper GM. Update on the management of chronic kidney disease. Am Fam Physician. 2012 Oct 15;86(8):749-754.

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