Year : 1994 | Volume
: 5 | Issue : 2 | Page : 179--183
Chronic Tubulo-interstitial Nephropathy with Hepatic Involvement in Children
Abdullah A Al-Salloum
Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Abdullah A Al-Salloum
Department of Pediatrics, College of Medicine, King Saud University, Riyadh
The clinical, biochemical and histological data are reported in a female infant with rapidly progressive renal failure, hepatosplenomegaly and death at the age of 2 years. This case represents another example of the newly described entity «DQ»chronic tubulointerstitial nephritis with hepatic involvement«DQ» and the only reported case of this kind from this part of the world.
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Al-Salloum AA. Chronic Tubulo-interstitial Nephropathy with Hepatic Involvement in Children.Saudi J Kidney Dis Transpl 1994;5:179-183
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Al-Salloum AA. Chronic Tubulo-interstitial Nephropathy with Hepatic Involvement in Children. Saudi J Kidney Dis Transpl [serial online] 1994 [cited 2020 Aug 4 ];5:179-183
Available from: http://www.sjkdt.org/text.asp?1994/5/2/179/41346
Autosomal recessive polycystic kidney disease and juvenile nephronophthisis are two known causes of end stage renal failure (ESRF) with hepatic involvement in childhood , . Autosomal recessive polycystic kidney disease is often divided into four subtypes based on the severity of renal and hepatic involvement  . Juvenile nephronophthisis rarely presents before 4 years  and may be associated with extra renal manifestations such as retinal dysplasia, skeletal and neuro-cutaneous abnormalities and hepatic fibrosis , . Progressive tubulo-interstitial nephropathy with hepatic involvement is a newly recognized entity which leads to end stage renal failure in infancy and early childhood ,,,,, . This report describes a clinical, biochemical and histological data from a female patient which shares many similarities with the previously described patients suffering from chronic interstitial nephropathy with hepatic involvement.
A 10 month old girl, the first child of parents of non-consanguineous marriage, was well till 6 months of age when she was noticed to be pale with generalized weakness, progressive loss of appetite, occasional vomiting and inadequate weight gain. She was born at term with a birth weight of 3 kg, after an uneventful pregnancy and delivery. Investigations in a private clinic at that time, demonstrated a normocytic normochromic anemia, with hemoglobin of 80 gm/L and reticulocyte count of 0.8%. Her anemia progressed in the face of full therapeutic trial with elemental iron. Therefore, she was referred to King Khalid University Hospital at 10 months of age for investigation of her anemia. She was pale and both her height and weight were below the third percentile for her age. The blood pressure was 130/85 mm Hg. The liver and spleen were enlarged and firm, 4 cm and 2 cm below the costal margin, respectively. There were scratch marks all over the trunk. Laboratory evaluation [Table 1] disclosed anemia, metabolic acidosis, high serum urea and creatinine as well as elevated serum transaminases and alkaline phosphatase. Results of viral hepatitis screen were negative. Early morning urine specific gravity was 1.005. The urine sediment had no cells, formed elements or crystals. Renal ultrasound showed bilaterally normal sized kidneys with increased parenchymal echogenicity, and loss of corticomedullary differentiation without evidence of obstruction. Computerized tomography (CT) scan of the abdomen revealed no cysts in the liver, spleen, pancreas or kidneys. Xray of hand and wrist showed evidence of renal osteodystrophy. Two weeks after admission, she underwent a percutaneous renal biopsy which was processed using routine methods. Special stains including, periodic acid schiff diastase, silver stain, congo red and Perl's stain were performed. Immunofluorescent and electron microscopic examinations were also performed. Renal biopsy [Figure 1] showed both medulla and cortex in which the glomeruli were immature and shrunken. There was Bowman's space dilatation due to periglomerular fibrosis. There was mesangial expansion in the glomeruli. Some of the tubules showed moderate to severe tubular atrophy with significant dilatation. The dilated tubules were lined by low cuboidal epithelium, but the site of origin of these dilated tubules could not be identified. The interstitium showed moderate to severe interstitial fibrosis with chronic inflammatory infiltrates. The small arteries and arterioles exhibited luminal narrowing with medial hypertrophy and mild fibrotic changes in them. Immunofluorescent study showed no significant staining for immunoglobulins and compliments. In addition, electron microscopic examination showed no specific glomerular or tubular change.
At 11 months of age she was started on continuous ambulatory peritoneal dialysis (CAPD), in addition to high caloric diet, calcitriol, calcium carbonate, water soluble multivitamins and captopril. She remained reasonably well, but continued to have hepatosplenomegaly and persistently raised liver enzymes. At the age of 18 months, she underwent liver biopsy [Figure 2] which was processed using routine methods. The biopsy showed preserved architecture of the parenchyma with periportal fibrosis and inflammatory infiltrates. There was bile duct proliferation and hepatocyte acinar formation. The inflammation was confined to the portal region and consisted of mononuclear infiltrate and scattered occasional polymorphonuclear cells. No hepatocyte necrosis was present, however, there was evidence of hepatocyte injury due to fibrosis and mononuclear inflammatory infiltrate. There was also evidence of bridging between the portal trial by fibrous tissue.
She was diagnosed to have progressive tubulo-interstitial nephropathy with hepatic involvement, based on her clinical presentation and course as well as the histological findings which were consistent with this newly described entity. Since, some of these patients have been successfully transplanted  , she was sent to USA for renal transplantation. Unfortunately, she died 4 months later because of peritonitis and septicemia at the age of 2 years.
The case presented here shares many similarities with the previously reported cases of the progressive tubulo-interstitial nephropathy with hepatic involvement in infancy and is the only case report of this kind from this part of the world ,,,,, . This child presented to the hospital with severe anemia, rapidly progressive renal failure requiring dialysis during the first year of life. The kidney biopsy showed dilatation of Bowman's space as well as proximal and distal tubules with moderate to severe interstitial fibrosis and chronic inflammatory infiltrates. She also had persistent hepatosplenomegaly and moderately raised liver transaminases. The liver biopsy showed periportal fibrosis and inflammatory infiltrates which were confined to the portal region. The histological features as well as most of the clinical features are shared with the previously reported 14 patients [Table 2].
It was argued previously that those cases may represent varieties of either infantile polycystic kidney disease with congenital hepatic fibrosis or cases of juvenile nephronophthisis ,, . It is true that some of the histological features resemble the changes found in infantile polycystic kidney disease with congential hepatic fibrosis but the finding of pronounced tubulo-cystic changes with extensive interstitial fibrosis and tubular atrophy (late lesion), as well as the evidence of hepatocyte injury cast doubt whether this category is appropriate. The youngest patient with infantile polycystic kidney diseases showing the "late lesion" was 26 months of age  .
The diagnosis of juvenile nephronophthisis (JNN) has also been suggested for such cases. The condition is usually characterized by insidious renal failure, hyposthenuria, poly-uria, failure to thrive. There is usually severe anemia but no hematuria, significant proteinuria, arterial hypertension or urinary infection. It is usually inherited in an autosomal recessive pattern  . It occurs mainly in children and usually leads to ESRF in the second decade of life. A few cases have been documented in infancy ,, .
Nephronophthisis in most cases, is an exclusive renal disease but may be associated with extra renal lesions such as retinal dysplasia and portal fibrosis , . The diagnostic histopathological changes include tubular degeneration and acellular interstitial fibrosis. There is thickening and splitting of the basement membrane which is now recognized as the most important feature ,,, . Our case as well as most of the reviewed cases differ from patients with JNN by, the age of onset, the presence of hypertension as well as the findings of cortical microcysts originating from proximal tubules and Bowman's spaces and the lack of thickening, wrinkling and splitting of the tubular basement membranes making the diagnosis JNN unlikely.
We concur with the conclusion made by others ,,, that these patients including ours represent a distinct entity which should be considered in the differential diagnosis of ESRF in infancy and early childhood. The features of this new entity include early clinical onset and rapid progression of renal failure or death before 2 years of age. It is usually associated with anemia, polyuria, failure to thrive, hepatomegaly, raised liver enzymes and hypertension. The condition is most likely transmitted in an autosomal recessive pattern because of the positive family history. In some cases renal transplantation is possible , but the long term prognosis post renal transplantation cannot be assessed at this point of time.
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