Adult Nephrotic Syndrome
This clinical case study will focus on a nephrotic syndrome (NS) and the most common complications in an adult patient population. Literature review of the most recent sources was performed to investigate the available information regarding the condition (pathophysiology, epidemiology and prevalence, diagnostics, physical exam findings, evidence-based treatment options, patient education, and so forth).
Nephrotic syndrome may affect anybody from infancy to older adults, but it is known to mostly target school-aged children and adolescents. The prevalence of the disease is close to 16 events per hundred thousand children, where males get affected two times more often than females in early childhood (Andolino & Reid-Adam, 2015). Nephrotic syndrome occurs due to excessive excretion of protein in urine because of alterations in the integrity of the glomerular filtration barrier. The main mechanism of the massive protein loss is increased glomerular permeability. The loss can be selective (albumin only) or nonselective (including most serum proteins), and such selectivity is an important distinction in diagnosis. The classic definition of nephrotic syndrome is massive proteinuria with 3 to 4 + protein with urinalysis; hypoalbuminemia (less than 2.5 g/dL), edema, and hyperlipidemia. Edema formation results from a decrease in the plasma oncotic pressure due to a loss of serum albumin, which causes water to leak into the interstitial space. This then leads to decreased intravascular volume with decreased renal perfusion and activation of the renin-angiotensin system (RAS). With protein loss, the liver increases the synthesis of protein and thereby causes concurrent hyperlipidemia and lipiduria. In addition, the reduced intravascular volume stimulates antidiuretic hormone, which enhances the reabsorption of water. Nephrotic syndrome can be congenital, idiopathic, or secondary (Gaylord, 2017).
The case study described in this paper is unique for several reasons. Although NS mostly affects children as a result of genetic, immune, systemic, nephrotoxic, allergic, malignant, or idiopathic processes; the patient in this case is a previously healthy adult. The complications of the syndrome that this patient has encountered could have been lethal, therefore the awareness of potential co-morbidities among primary care providers and the knowledge of diagnostic workup may save a life in the future.
Patients affected by nephrotic syndrome will often develop venous thrombosis, especially deep vein thrombosis and renal vein thrombosis; pulmonary embolism also occurs frequently, as well as cerebral venous thrombosis. Adult patients may also encounter arterial thromboses associated with NS. The reason for the hypercoagulable condition in patients with NS is poorly understood to this date.
Summary of the patient presentation: Assessment
Date and Time of History: November 1st, 2016 9:00 AM
Identifying Data: J. S. is a 22-year-old female patient who is single. She is a full-time university student. She was not referred by anyone to the clinic.
Reliability: J. S. is able to describe her history and symptoms in clear and precise manner. She is well groomed and dressed. Appears cooperative, friendly and reliable.
“I’ve been having leg swelling for the past two weeks and thought it was unusual for me, but it wasn’t until last night where my heart started racing and chest was hurting, I got scared and called the office for an appointment.”
History of present illness
Patient presents to the clinic complaining of chest pain and palpitations. This is a new problem for her. She also reports bilateral lower extremity edema for the past two weeks.
Patient does not take any daily medications.
No known drug allergies.
Patient does not drink alcohol. She denies using any oral, nasal, or injection drugs.
Patient denies using tobacco.
Childhood Illnesses: Chicken pox when patient was 3 years old. No other illnesses reported.
Adult Illnesses. Medical: No significant history as an adult. Surgical: None reported. Ob/Gyn: Menarche at 13 years old. Regular menstrual cycle 26 days. No other history reported. Psychiatric: None reported.
Family History: Mother is 56 years old and has hyperlipidemia and migraine headaches. Father is 59 years old and has hypertension and gout. Brother is 27 and is in good health. Sister is 29 and has frequent UTIs and kidney stones.
Health Maintenance: Patient maintains a healthy diet and consumes a lot of vegetables and fruit. She jogs 3 times a week for at least 2-3 miles. All immunizations are up-to-date. Patient wears seat belt while driving.
Personal and Social History: J. S. is an overall healthy Asian female. She is in stable economic condition. She lives with two roommates on university campus. Patient is sexually active and prefers men. Patient denies recent travels overseas.
Review of Systems
General: Patient denies changes in weight, chills and night sweats. Complaints of chest pain that is 4 out of 10.
Skin, Hair, Nails: Denies changes in skin color, dryness, changes in hair and nails.
Head, Eyes, Ears, Nose, and Throat (HEENT): Denies headache, head injury, dizziness, and lightheadedness. Patient denies blurred vision, itchiness, redness, and pain. Last eye examination was three years ago. Patient does not wear glasses. She denies hearing deficit, pain, tinnitus, vertigo or recent ear infections. Denies frequent colds, nasal stuffiness, mucous yellow-green discharge, and sinus tenderness. Denies hay fever and nose bleeds. She maintains good oral health. Denies bleeding gums and dry mouth. Last dental exam 6 months ago.
Respiratory: Denies cough, dyspnea, and/or wheezing. Denies history of lung disease, tuberculosis and pneumonia.
Cardiovascular: Positive for chest pain and palpitations for 2 days. Denies heart disease, elevated blood pressure, dyspnea, and orthopnea. Denies any cardiac tests in the past. Denies intermittent claudication, leg cramps, and varicose veins. Positive for swelling in both legs for past two weeks. No change in color in fingertips or toes during cold weather reported. No history of varicose veins or phlebitis.
Gastrointestinal: Denies nausea and vomiting, heartburn, pain, gallbladder or liver problems. Denies diarrhea or constipation. Reports good appetite.
Urinary: Denies frequency of urination, polyuria, hematuria, flank pain, incontinence, burning, and urgency. Denies history of kidney stones.
Musculoskeletal: Denies history of join disease, past injuries, arthritis, or gout. Denies pain, stiffness, weakness, and swelling of extremities except the left knee. Pt denies any musculoskeletal pain, cramping, gait problems. Left knee pain present. See HPI.
Neurologic: Denies changes in mood and attention, fainting, seizures, motor or sensory loss, memory loss, and tremors.
Endocrine: Denies thyroid problems, temperature intolerance, excessive sweat and hunger (Bickley & Szilagyi, 2013).
General: Twenty-two-year-old overall healthy female, who is alert and oriented x4; she maintains good eye contact, engaging with the provider. Appears to be well nourished and groomed. She does have ill appearance and slightly anxious during this visit.
Vital Signs: T 36.7°C, HR 120, RR 20, BP 112/64, O2 97% on room air. Height 166 cm, weight 53 kg.
Skin, Hair, Nails: Skin is warm, well-hydrated, without rash. Good turgor and mobility, without bruising or lesions. Hair evenly distributed, normal texture, no alopecia present. Nails without clubbing and cyanosis. Capillary refill is 2 seconds (Bickley & Szilagyi, 2013).
HEENT: Normocephalic/atraumatic head, no visible or palpable masses. No depressions, lesions, tenderness, scaling, or scaring noted on the scalp. Face symmetrical without abnormal facial structures. Vision 20/20. Eyes without exophthalmos. White sclera. Conjunctiva is pink and moist. Eyes PERRLA. Normal optic discs and vessels, no exudates, papilledema, and hemorrhage. Positive red reflex bilaterally. Ears are equal is size and symmetrical, without tenderness, swelling, or drainage. Tympanic membranes are silver-grey color, translucent, mobile, no redness or fluid accumulation found. No nasal flaring observed. Nasal mucosa not inflamed, no septal deviation observed. Oral mucosa is moist and pink, no lesions noted. Oropharynx is pink without inflammation. Uvula is midline, positive gag reflex. Gums are pale and intact. Good dental health. (Bickley & Szilagyi, 2013).
Thorax and Lungs: Skin intact and warm. Thorax symmetric with good excursion. Respirations even, unlabored and effortless. Chest wall intact, no tenderness, no masses or lesions. No tactile fremitus present. Resonance heard on percussion. Lungs are clear in all fields auscultated anteriorly and posteriorly. No adventitious breath sounds heard. Bronchophony, egophony, and whispered pectoriloquy negative. No accessory muscle use (Bickley & Szilagyi, 2013).
Cardiac/Peripheral Vascular: Jugular venous pressure 2 cm above the sternal angle with the head of bed raised to 30 degrees. Carotid upstrokes brisk without bruits; strong amplitude. No visible pulsations, no heave, or lift noted on the inspection. Point of maximum impulse is not palpable. Heart rate 98 beats per minute with regular rhythm. Good S1, S2, no S3, or S4. No murmur, thrills, or gallop. No cardiomegaly. No discoloration in hands or feet on inspection. No varicose veins, thrombophlebitis, or ulcers noted. Radial, brachial, femoral, popliteal, dorsalis pedis, posterior tibial pulses present and easily palpable, 2+ and equal bilaterally, brisk, rhythm regular. Allen test is negative bilaterally in both radial and ulnar arteries. No lymphadenopathy. Bilateral lower extremity edema +2 noted. No pain or tenderness in calves. Homan’s sign is negative bilaterally. No venous insufficiency noted. No stasis pigmentation or ulcers (Bickley & Szilagyi, 2013).
Abdomen: Flat and symmetric. Bowel sounds active in all four quadrants. No tenderness or masses noted. No hepatosplenomegaly seen. Spleen and kidneys not felt. No costovertebral angle tenderness. No umbilical hernia observed. No audible bruits over abdominal arteries heard (Bickley & Szilagyi, 2013).
Genitourinary. No costovertebral tenderness present. Kidneys are not palpable.
Musculoskeletal: All extremities are warm dry and intact. No gait disturbances present. No joint deformities or visible asymmetry present. Full range of motion present in all extremities. Muscle strength to all extremities is equal bilaterally 5/5 (Bickley & Szilagyi, 2013).
Neurological: Patient is alert and oriented to person, place, time and situation. Appropriate response, coherent. Eyes PERRLA. Cranial nerves II-XII are intact.
Laboratory Data: WBC 9660 cells/μL; Hgb 13.9g/dL; Hct 41%; Pl 331,000/μL; BUN 18mg/dL; Cr 1.24 mg/dL; serum albumin 1.6g/dL; total protein 4.4 g/dL; total chol. 485 mg/dL; Trig. 179 mg/dL; ANA negative; PT 14.9; APTT 83.8 seconds; D-dimer 6.8 μg/mL; fibrinogen 829 mg/mL; FDP 10.5 μg/dL; antithrombin III 69%; protein C 30%; and protein S 67%. Urinary protein excretion was 14g/g creatinine, urinalysis negative for hematuria. ABG: pH 7.45, PaCO2 35.3 mmHg, PaO2 88.4 mmHg, and HCO3 26 mEq/L. ECG normal. CXR negative for any abnormalities. Computed tomography (CT) angiogram showed bilateral pulmonary artery thrombi as well as left common iliac vein thrombus. The like hood of pulmonary thrombosis originating from the blockage in left iliac vein was found to be high.
Diagnostic studies used in this patient were geared towards kidney function due to edema in lower extremities, as well as cardiac function due to patient’s chest pain and palpitations. It is recommended to perform urinalysis (UA) and microscopic examination (proteinuria, microhematuria, elevated specific gravity, fat bodies, and casts are expected). Also, 24-hour collection or protein-creatinine ratio on a random first-morning urine is needed. Recommended blood tests include CBC, CMP, BUN, creatinine, calcium serum albumin, total protein, liver enzymes, triglycerides, lipoproteins, cholesterol, C3 and C4, and ANA (Gaylord, 2017).
Protein in the urine, hypoalbuminemia, along with peripheral edema is typically sufficient to diagnose the nephrotic syndrome. High cholesterol levels and thrombosis are often seen as well. Among the differential diagnoses are:
- Heart failure (patient will commonly have history of heart disease, fluctuations in blood pressure, S3 heart sound, absence of proteinuria, edema, shortness of breath along with crackles upon auscultation, cough and/or wheezing, and others) (American Heart Association, 2017).
- Glomerulonephritis (patient may present with elevated blood pressure, dark urine, hematuria, edema, headache, fatigue, fever, abdominal or flank pain, jugular vein distention, adventitious lung sounds, and others) (Kawasaki, 2012).
- Focal segmental glomerulosclerosis (nearly 70% of patients will have NS; patients present with edema that is hard to manage, large proteinuria, hypoalbuminemia, elevated cholesterol, hypertension, rapid loss of renal function, ascites, pain, and others) (Rosenberg & Kopp, 2017).
- Minimal change disease (patients typically present with proteinuria, edema, foamy urine, poor appetite, weight gain, fatigue, high cholesterol, hypoalbuminemia, and others) (Mason & Hoyer, 2015).
Development of treatment plan
There are very few non-pharmacological modalities that can be helpful for patient with nephrotic syndrome. Among those are: restriction of protein, sodium restriction (less than 2 grams per day), fluid restriction, dietary modifications for hyperlipidemia, and extremity elevation to reduce the swelling. Nephrotic syndrome with pulmonary artery thrombosis would require some aggressive pharmacological and sometimes surgical modalities. Corticosteroids are the backbone of NS treatment. Prednisone 60mg/m2/day for six weeks, and then switching to 40mg/m2/day on alternate days for two-to-five months with tapering. Steroid treatment is recommended for the minimum of 12 weeks. In addition to corticosteroids patient may be treated with simvastatin, gemfibrozil, and cholestyramine to treat hyperlipidemia. In case of severe edema that is not controlled with diet and fluid restriction, consider administering albumin and Lasix. Providers may consider calcium and vitamin D supplementation to prevent osteoporosis. Additionally, angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) can be initiated to decrease the waste of protein in the urine (Nishi, et al., 2016).
In order to treat hypercoagulability in NS, provider will order anticoagulation to prevent events like pulmonary embolism and deep vein thrombosis, thrombolytic therapy, thrombectomy in some cases, and inferior vena cava (IVC) filter placement. In this case study, J. S. was treated with intravenous heparin and urokinase, oral Coumadin for 6 months after hospital discharge, and had IVC filter placed in the hospital. Following the complicated inpatient and outpatient treatment, nephrotic syndrome symptoms were resolved within three weeks of corticosteroid therapy. Repeat contrast CT two weeks after the initiation of treatment showed a reduction in pulmonary thrombi and capture of iliac vein thrombus in IVC filter. The fast and full recovery following steroid therapy pointed towards the minimal change disease as the etiology of nephrotic syndrome and thrombus of pulmonary artery.
Patient education should involve all information regarding the nephrotic syndrome and the associated complications. Infection monitoring and prompt treatment is essential because infection is a major complication of NS. Patient must report any fever to the provider. Patients are recommended to get flu vaccine every year. Additionally, patient and family education should stress the importance of an ongoing and regular care to monitor kidney function and the early treatment of any complications. Patient should be informed of a potential relapse. An understanding of the disease process, steroid side effects, recognition of an infection, and monitoring for proteinuria is vital. Patients and families can be reassured that any residual renal dysfunction is possible but unlikely (Gaylord, 2017).
Follow-up and evaluation of the patient status
Patients presenting with protein in their urine and hypercoagulability symptoms must be admitted to a hospital and promptly referred to the nephrology team. Although most kidney specialist are familiar with all complications of the NS, cardiology should be consulted as well. In case a patient is not responding to corticosteroid therapy favorably, a renal biopsy may be warranted. Anticoagulation therapy needs to be suspended prior to the procedure. Daily home proteinuria testing is recommended to monitor the patient and identify exacerbations. Relapse is defined as protein in the urine (2+ or greater) for three days. Home blood pressure monitoring is warranted as well (Gaylord, 2017).
Patients should undergo routine testing for serum creatinine, BUN, and urinalysis at least every 6 months. Those taking immunosuppressant medications and steroids should be regularly evaluated for complications of treatment. This includes blood pressure, weight, and growth monitoring at each visit to exclude hypertension, growth failure, and morbid obesity, potential complications of repeated corticosteroid therapy. In addition, a CBC to evaluate for blood dyscrasias, and a complete metabolic panel to evaluate for liver function and electrolyte abnormalities should be performed to exclude consequences of immunosuppressant therapy.
In conclusion, this case study discussed a 21-year old Asian woman who presented with nephrotic syndrome and pulmonary artery thrombosis as the major complication. Computed tomography scan with contrast played a vital role in diagnosing this problem. The knowledge of potential hypercoagulability in NS among primary care providers is essential and can save many lives.
American Heart Association. (2017). Warning signs of heart failure. Retrieved from http://www.heart.org/HEARTORG/Conditions/HeartFailure/WarningSignsforHeartFailure/Warning-Signs-for-Heart-Failure_UCM_002045_Article.jsp#.WhimcLT83OQ
Andolino, T. P., & Reid-Adam, J. (2015). Nephrotic syndrome. Pediatrics in Review, 36(3) 117-126.
Gaylord, N. M. (2017). Genitourinary disorders. In C. E. Burns, A. M. Dunn, M. A. Brady, N. B. Starr, C. G. Blosser & D. L. Garzon (Eds.), Pediatric Primary Care. (pp. 911-947). St. Louis, MO: Elsevier.
Kawasaki, Y. (2012). Mechanism of onset and exacerbation of chronic glomerulonephritis and its treatment. Pediatr Int., 53(6), 795-806.
Kerlin, B. A., Ayoob, R., & Smoyer, W. E. (2012). Epidemiology and pathophysiology of nephrotic syndrome – associated thromboembolic disease. Clinical Journal of the American Society of Nephrology, 7(3), 513-520.
Kerlin, B. A., Waller, A. P., Sharma, R., Chanley, M. A., Nieman, M. T., & Smoyer, W. E. (2015). Disease severity correlates with thrombotic capacity in experimental nephrotic syndrome. Journal of the American Society of Nephrology, 26(12), 3009-3019.
Mason, P. D., & Hoyer, P. F. (2015). Minimal change nephrotic syndrome. Comprehensive Clinical Nephrology. (5th ed.). Philadelphia, PA: Elsevier Saunders.
Nishi, S., Ubara, Y., Utsunomiya, Y., Okada, K., Obata, Y., Kai, H., & Matsuo, S. (2016). Evidence-based clinical practice guidelines for nephrotic syndrome 2014. Clinical and Experimental Nephrology, 20, 342–370.
Rosenberg, A. Z., & Kopp J. B., (2017). Focal Segmental Glomerulosclerosis. Clin J Am Soc Nephrol, 12(3), 502-517.
Singhal, R., & Brimble, K. S. (2006). Thromboembolic complications in the nephrotic syndrome: Pathophysiology and clinical management. Thrombosis research, 118(3), 397-407.