The first step in the differential diagnosis of CKD is establishing its chronicity, i.e., disproving a major acute component. The two most common means of determining disease chronicity are the history and prior laboratory data (if available) and the renal ultrasound, which is used to measure kidney size. In general, kidneys that have shrunk (<10–11.5 cm, depending on body size) are more likely affected by chronic disease. While reasonably specific (few false positives), reduced kidney size is only a moderately sensitive marker for CKD, i.e., there are several relatively common conditions in which kidney disease may be chronic without any reduction in renal size. Diabetic nephropathy, HIV-associated nephropathy, and infiltrative diseases such as multiple myeloma or amyloidosis may in fact be associated with relatively large kidneys despite chronicity. Renal biopsy, although rarely performed in pts with CKD, is a more reliable means of proving chronicity; a predominance of glomerulosclerosis or interstitial fibrosis argues strongly for chronic disease. Hyperphosphatemia, anemia, and other laboratory abnormalities are not reliable indicators in distinguishing acute from chronic disease.
Once chronicity has been established, clues from the physical examination, laboratory panel, and urine sediment evaluation can be used to determine etiology. A detailed history will identify important comorbid conditions, such as diabetes, HIV seropositivity, or peripheral vascular disease. The family history is paramount in the workup of autosomal dominant polycystic kidney disease or hereditary nephritis (Alport’s syndrome). An occupational history may reveal exposure to environmental toxins or culprit drugs (including over-the-counter agents, such as analgesics or Chinese herbs).
Physical examination may demonstrate abdominal masses (i.e., polycystic kidneys), diminished pulses or femoral/carotid bruits (i.e., atherosclerotic peripheral vascular disease), or abdominal or femoral bruits (i.e., renovascular disease). The history and examination may also yield important data regarding severity of disease. Excoriations (uremic pruritus), pallor (anemia), muscle wasting, and a nitrogenous fetor are all signs of advanced CKD, as are pericarditis, pleuritis, and asterixis, complications of particular concern that usually prompt the initiation of dialysis.
Serum and urine laboratory findings typically provide additional information useful in determining the etiology and severity of CKD; serial studies determine the pace of progression and/or whether the renal failure is in fact acute. Heavy proteinuria (>3.5 g/d), hypoalbuminemia, hypercholesterolemia, and edema suggest nephrotic syndrome (Chap. 142). Diabetic nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, minimal change disease, amyloid, and HIV-associated nephropathy are principal causes. Proteinuria may decrease slightly with decreasing GFR, but rarely to normal levels. Hyperkalemia and metabolic acidosis may complicate all forms of CKD eventually, but can be more prominent in pts with interstitial renal diseases. Serum and urine protein electrophoresis, in addition to serum free light chains, should be obtained in all pts >35 years of age with CKD to exclude paraproteinemia-associated renal disease. If underlying glomerulonephritis is suspected, autoimmune disorders such as lupus and infectious etiologies such as hepatitis B and C should be assessed. Serum concentrations of calcium, phosphate, vitamin D, and parathyroid hormone (PTH) should be measured to evaluate metabolic bone disease. Hemoglobin, vitamin B12, folate, and iron studies should be measured to evaluate anemia.