Symptoms, signs, and differential diagnosis

2.1 Edema

2.1.1 Renal

Probable Diagnosis	Symptoms/Signs	Diagnostic Procedures
Nephrotic syndrome	• Facial swelling • Swelling of the arms and legs, especially the ankles and feet • Pleural effusions • Foamy urination • Weight gain (water retention)	• Urine protein/Cr ratio or 24-hour urine protein • BUN • Serum Cr • Serum albumin • CrCl or eGFR • UA with sediment microscopy • Serum and urine protein electrophoresis • HIV, anti-PLA2R (for membranous nephropathy) and hepatitis antibodies • Renal biopsy
Nephritic syndrome (e.g., acute glomerulonephritis)	• Peripheral or periorbital edema • Hematuria • Oliguria • Headache, secondary to hypertension • Shortness of breath or dyspnea on exertion, secondary to heart failure • Possible flank pain, secondary to stretching of the renal capsule	• UA and urinary sediment for protein, RBCs, acanthocytes, WBCs, casts (e.g., RBC casts) • Serum electrolytes, BUN, Cr • Serological tests for C3, C4, ASLO, ANCA, anti-GBM, and hepatitis antibodies • Serum and urine protein electrophoresis • Renal US and renal biopsy
CKD	• Swelling: generalized (fluid retention), ankle, foot, and leg • High blood pressure • Nausea or vomiting • Loss of appetite • Metallic taste in mouth • Flank pain • Hyperkalemia, metabolic acidosis • Urination changes: oliguria, anuria, nocturia (excessive urination at night) • Fatigue	• Blood tests: Cr, BUN, electrolytes, CBC, calcium, phosphate, albumin • CrCl or eGFR • Urine tests: 24-hour urinary protein or urine protein to Cr ratio • Serum and urine protein electrophoresis • Arterial or venous blood gas, if serum bicarbonate is low • Renal US • Renal biopsy if indicated and kidneys are not contracted and small • Abdominal CT scan or MRI when indicated by US findings

ASLO , antistreptolysin O; ANCA , anti-neutrophil cytoplasmic autoantibody; BUN , blood urea nitrogen; C3 , C3 complement; C4 , C4 complement; CBC , complete blood count; CKD , chronic kidney disease; Cr , creatinine; CrCl , creatinine clearance; eGFR , estimated glomerular filtration rate; GBM , glomerular basement membrane; PLA2R , phospholipase-A2 receptor; RBCs , red blood cells; UA , urinalysis; US , ultrasound; WBCs , white blood cells.

2.1.2 Cardiovascular

Probable Diagnosis	Symptoms/Signs	Diagnostic Procedures
Congestive heart failure (CHF)	• Swelling (edema) of the ankles and legs or abdomen • Basilar lung crackles • S3 gallop • Dyspnea (shortness of breath) • Cough • Fatigue, weakness, faintness • Loss of appetite • Palpitations • Swollen (enlarged) liver or abdomen • Neck veins distended • Nocturia (increased urination at night) • Weight gain	• ECG • Echocardiogram (echo) • Chest X-ray • Cardiac catheterization and angiography, if indicated • Blood test: BNP level
Cardiomyopathy (largely similar to CHF)	• Shortness of breath or dyspnea with physical exertion • Chest pain • Fatigue (tiredness) • Swelling in the ankles, feet, legs, abdomen, and veins in the neck • Dizziness, fainting • Lightheadedness • Arrhythmias (irregular heartbeats) • Heart murmurs	• Physical examination (tachypnea, tachycardia, hypertension or hypotension, hypoxia, JVD, pulmonary edema (lung crackles and/or wheezes), S3 gallop • BNP • Chest X-ray, MRI • Cardiac catheterization

BNP , Brain natriuretic peptide; CHF , congestive heart failure; ECG , electrocardiogram; JVD , jugular venous distension.

2.1.3 Endocrine

Probable Diagnosis	Symptoms/Signs	Diagnostic Procedures
Cushing syndrome	• Round, red, full face (moon face) • Cervical fat pads • Comedones (acne) • Purplish pink stretch marks (abdominal striae) • Fatigue, headache, weak muscles • High blood pressure, high blood sugars, hypokalemia • Polydipsia and polyuria • Loss of libido, depression	• Clinical evaluation • Serum and salivary cortisol level, ACTH levels • Dexamethasone suppression test • 24-hour urinary measurement for cortisol • Abdominal CT or MRI scan of adrenal glands and MRI of pituitary gland • Bone density test
Hypothyroidism	• Puffy face and hands, and swelling of the legs • Increased sensitivity to cold • Fatigue or feeling slowed down • Joint or muscle pain • Coarse hair or brittle fingernails • Dry skin • Muscle cramps	• Clinical evaluation • TFTs • TRH test • MRI of the brain
Hyperthyroidism	(see 2.2 Hypertension )

ACTH , Adrenocorticotropic hormone; TFTs , thyroid function tests; TRH , thyroid releasing hormone.

2.1.4 Others

Probable Diagnosis	Symptoms/Signs	Diagnostic Procedures
Cirrhosis	• Swelling or fluid buildup of the legs (edema) and in the abdomen (ascites) • Confusion or problems thinking (hepatic encephalopathy) • Loss of appetite • Nausea and vomiting • Nosebleeds or bleeding gums • Pale or clay-colored stools • Small, red, spider-like blood vessels on the skin (spider angiomas) • Yellow color in the skin, mucus membranes, or eyes (jaundice) • Impotence, loss of libido	• Clinical history (alcoholism, obesity, hepatitis B or C, type 2 diabetes) • CBC, LFTs • Abdominal US • CT or MRI of the abdomen, hepatic fibrosis scan • Endoscopy to check abnormal variceal veins in the esophagus or stomach • Liver biopsy confirming cirrhosis/etiology • Levels of AFP • Wilson’s disease, hemochromatosis studies, if indicated
Preeclampsia	• Swelling of face or legs • Severe headaches • Hypertension • Hyperreflexia • Blurry vision, flashing lights, or floaters • Vomiting, pain in the upper abdomen • Decrease in urine output	• CBC with differential and platelet count • Check for proteinuria • 24-hour urine collection for CrCl and total protein • Fetal US • sFLT-1 level or sFLT-1:PIGF ratio when diagnosis is unclear • LFTs (acute fatty liver of pregnancy)

AFP , Alpha-fetoprotein; CBC , complete blood count; CrCl , creatinine clearance; LFTs , liver function tests; US , ultrasound.

2.2 Hypertension

Probable Diagnosis	Symptoms/Signs	Diagnostic Procedures
CKD	(see 2.1.1 Renal )
Hyperthyroidism	• High blood pressure • Difficulty concentrating • Fatigue • Frequent bowel movements • Goiter (visibly enlarged thyroid gland) or thyroid nodules • Heat intolerance • Increased appetite • Increased sweating • Itching (overall) • Lack of menstrual periods • Nausea and vomiting • Pounding, rapid, or irregular pulse • Protruding eyes (exophthalmos)	• Clinical evaluation • TFTs, thyroid scan • Radioactive iodine uptake • Blood glucose (hyperglycemia)
Cushing syndrome	(see 2.1.3 Endocrine )
Primary hyperaldosteronism (Conn’s syndrome)	• Hypertension • Muscle weakness • Polydipsia • Polyuria • Hypokalemia	• Blood test: plasma aldosterone/renin ratio • 24-hour urinary excretion of aldosterone test • Serum electrolytes for hypokalemia, metabolic alkalosis • Saline suppression test of aldosterone • MRI of adrenal glands • Adrenal vein sampling (to distinguish adenoma from bilateral hyperplasia) • Spironolactone therapeutic trial