Tubulointerstitial disorders can result from several metabolic disturbances.
Several metabolic disturbances can cause tubulointerstitial nephritis (see Tubulointerstitial Nephritis).
Acute urate nephropathy:
This disorder is not a true form of acute tubulointerstitial nephritis but rather an intraluminal obstructive uropathy caused by uric acid crystal deposition within the lumen of renal tubules; acute oliguric or anuric kidney injury results. Causes include the following:
Typically, no symptoms are present. Diagnosis is suspected when acute kidney injury occurs in patients with marked hyperuricemia (> 15 mg/dL). Urinalysis results may be normal or may show urate crystals.
Prognosis for complete recovery of renal function is excellent if treatment is initiated rapidly. In patients with normal cardiac and renal function, treatment is usually with allopurinol plus aggressive IV hydration with normal saline. Supportive measures are indicated. Hemodialysis may be recommended to remove excess circulating urate in severe cases where diuresis cannot be induced with a loop diuretic and IV saline. Alkalinization with a NaHCO3 infusion is no longer recommended because even though it increases solubility of urate, it risks tubular precipitation of Ca phosphate salts.
Prevention is indicated for patients at high risk (eg, those at risk of tumor lysis syndrome). Prevention is by use of allopurinol 300 mg po bid to tid plus saline loading to maintain a urine output > 2.5 L/day before chemotherapy or radiation therapy. Urate oxidase (rasburicase), which catalyzes urate to a much more soluble compound, is also preventive and is being more commonly used in patients with severe hyperuricemia. However, patients given rasburicase must be carefully monitored because the drug must be given IV and can cause anaphylaxis, hemolysis, and other adverse effects.
Chronic urate nephropathy:
This condition is chronic tubulointerstitial nephritis caused by deposition of Na urate crystals in the medullary interstitium in patients with chronic hyperuricemia. Sequelae are chronic inflammation and fibrosis, with ensuing chronic renal insufficiency and renal failure. Chronic urate nephropathy was once common in patients with tophaceous gout but is now rare because gout is more often effectively treated. A bland urine sediment and hyperuricemia disproportionate to the degree of renal insufficiency (eg, urate > 9 mg/dL with serum creatinine < 1.5 mg/dL, or > 10 mg/dL with serum creatinine 1.5 to 2 mg/dL, and > 12 mg/dL with more advanced renal failure) are suggestive but nonspecific; many causes of tubulointerstitial diseases may have these findings, lead nephropathy being the most common. Treatment is that of hyperuricosuria (see Lowering the serum urate level).
Hyperoxaluria is a common cause of nephrolithiasis but an uncommon cause of acute and chronic tubulointerstitial nephritis. Causes and prevention of hyperoxaluria are discussed elsewhere (see Urinary Calculi).
Hypercalcemia (see Hypercalcemia) causes nephropathy by 2 mechanisms. Severe (> 12 mg/dL) temporary hypercalcemia may cause reversible renal insufficiency by renal vasoconstriction and natriuresis-induced volume depletion. Long-standing hypercalcemia and hypercalciuria lead to chronic tubulointerstitial nephritis with calcification and necrosis of tubular cells, interstitial fibrosis, and calcification (nephrocalcinosis). Common associated findings include
Diagnosis is based on presence of hypercalcemia and unexplained renal insufficiency; nephrocalcinosis can be detected by ultrasonography or noncontrast CT. Treatment is management of hypercalcemia.
Chronic hypokalemia of a moderate to severe degree may cause nephropathy with impaired urinary concentration and vacuolation of proximal tubular cells and occasionally of distal tubular cells. Chronic interstitial inflammatory changes, fibrosis, and renal cysts have been found in renal biopsies of patients with hypokalemia of ≥ 1 mo. Treatment consists of correction of the underlying disorder and oral K supplements. Although the hypokalemia as well as the number and size of the cysts are reversible, the CTIN and renal insufficiency may be irreversible.
Last full review/revision March 2013 by Navin Jaipaul, MD, MHS
Content last modified September 2013