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Improved occupational and public health measures, together with the banning of over-the-counter phenacetin-containing analgesics, has led to a dramatic decline in the incidence of chronic interstitial nephritis (CIN) from heavy metal—particularly lead and cadmium—exposure and analgesic nephropathy in North America. Today, CIN is most often the result of renal ischemia or secondary to a primary glomerular disease (Chap. 308). Other important forms of CIN are the result of developmental anomalies or inherited diseases such as reflux nephropathy or sickle cell nephropathy and may not be recognized until adolescence or adulthood. Although it is impossible to reverse damage that has already occurred, further deterioration may be prevented or at least slowed in such cases by treating glomerular hypertension, a common denominator in the development of secondary FSGS and progressive loss of functioning nephrons. Therefore, awareness and early detection of patients at risk may prevent them from developing end-stage renal disease (ESRD).

VESICOURETERAL REFLUX AND REFLUX NEPHROPATHY

Reflux nephropathy is the consequence of vesicoureteral reflux (VUR) or other urologic anomalies in early childhood. It was previously called chronic pyelonephritis because it was believed to result from recurrent urinary tract infections (UTIs) in childhood. VUR stems from abnormal retrograde urine flow from the bladder into one or both ureters and kidneys because of mislocated and incompetent ureterovesical valves (Fig. 310-4). Although high-pressure sterile reflux may impair normal growth of the kidneys, when coupled with recurrent UTIs in early childhood, the result is patchy interstitial scarring and tubular atrophy. Loss of functioning nephrons leads to hypertrophy of the remnant glomeruli and eventual secondary FSGS. Reflux nephropathy often goes unnoticed until early adulthood when chronic kidney disease is detected during routine evaluation or during pregnancy. Affected adults are frequently asymptomatic, but may give a history of prolonged bed-wetting or recurrent UTIs during childhood, and exhibit variable renal insufficiency, hypertension, mild to moderate proteinuria, and unremarkable urine sediment. When both kidneys are affected, the disease often progresses inexorably over several years to ESRD, despite the absence of ongoing urinary infections or reflux. A single affected kidney may go undetected, except for the presence of hypertension. Renal ultrasound in adults characteristically shows asymmetric small kidneys with irregular outlines, thinned cortices, and regions of compensatory hypertrophy (Fig. 310-4).

FIGURE 310-4

Radiographs of vesicoureteral reflux (VUR) and reflux nephropathy. A. Voiding cystourethrogram in a 7-month-old baby with bilateral high-grade VUR evidenced by clubbed calyces (arrows) and dilated tortuous ureters (U) entering the bladder (B). B. Abdominal computed tomography scan (coronal plane reconstruction) in a child showing severe scarring of the lower portion of the right kidney (arrow). C. Sonogram of the right kidney showing loss of parenchyma at the lower pole due to scarring (arrow) and hypertrophy of the mid-region (arrowhead). (Courtesy of Dr. George Gross, University of Maryland Medical Center; with permission.)

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