Chronic Cholestatic Liver Disease With Associated Tubulointerstitial Nephropathy in Early Childhood

Abstract

ABSTRACT. We report the clinical and morphological features of an unusual hepatorenal disorder in 2 patients. The main clinical features were early onset of cholestatic liver disease and progressive tubulointerstitial nephritis, leading to renal death in early childhood. Renal histology showed interstitial fibrosis, tubular atrophy and dilatation, glomerular cysts in the cortex and periglomerular fibrosis; liver histology was characterized by portal fibrosis and bile duct abnormalities. Evaluating the 12 patients published in the literature, the long-term prognosis of the liver function appears bad, suggesting the possibility of a combined liver and kidney transplantation. Pediatrics 1997;100(3). URL: http://www.pediatrics. org/cgi/content/full/100/3/e10; cholestasis, tubulointerstitial nephritis, end-stage renal disease, liver and kidney transplantation, childhood.

Bile acids trigger cholemic nephropathy in common bile-duct-ligated mice

“…6,[44][45][46] Clinical features were comparable, including early onset of tubulointerstitial nephritis and cholestasis and a renal histology characterized by tubular atrophy/dilatation, and interstitial and periglomerular fibrosis, finally leading to end-stage renal disease. 5 Moreover, chronic cholestatic liver diseases have been reported to be associated with tubulointersti-tial nephritis and Fanconi's syndrome. [47][48][49] Severe alcoholic steatohepatitis carries a notoriously high risk for renal failure.…”

“…Interestingly, recent studies revealed a high proportion of structural abnormalities, including vascular and tubular epithelial injuries, on renal biopsies in patients with cirrhosis with impaired renal function without proteinuria and hematuria . In addition, chronic cholestatic liver diseases are frequently associated with tubulointerstitial nephropathies . Likewise, patients with obstructive jaundice have an increased incidence of AKI and renal failure in the perioperative phase and frequently show acute tubular epithelial injury on renal biopsy, despite careful volume replacement therapy .…”

“…3,4 In addition, chronic cholestatic liver diseases are frequently associated with tubulointerstitial nephropathies. 5,6 Likewise, patients with obstructive jaundice have an increased incidence of AKI and renal failure in the perioperative phase 7,8 and frequently show acute tubular epithelial injury on renal biopsy, despite careful volume replacement therapy. 4 Such renal alterations in cholestasis were previously also referred to as cholemic nephropathy.…”

Bile Acid-Induced Cholemic Nephropathy

“…For years, chronic cholestatic liver diseases have been reported to be associated with tubulointerstitial nephropathies such as tubulointerstitial nephritis and Fanconi syndrome (e.g. pediatric cholestatic syndromes, primary biliary cirrhosis, primary sclerosing cholangitis, drug-induced/steroid-induced cholestasis) [35,36,37,38,39,40,41]. Additionally, there are several reports on cholestatic liver diseases associated with progressive tubulointerstitial nephropathy as rare hepatorenal disorders and as a distinct entity in early childhood [35,36,42,43,44].…”

“…Additionally, there are several reports on cholestatic liver diseases associated with progressive tubulointerstitial nephropathy as rare hepatorenal disorders and as a distinct entity in early childhood [35,36,42,43,44]. Clinical features in all these cases were comparable, including early onset of tubulointerstitial nephritis in parallel with clinical and laboratory signs of cholestasis and a renal histology characterized by tubular atrophy and dilatation, as well as interstitial and periglomerular fibrosis finally leading to end-stage renal disease [37]. …”