Apoptosis contributes to amphotericin B-induced nephrotoxicity.

The aim of this study was to investigate whether apoptosis contributes to nephrotoxicity caused by amphotericin B (AmB). By detecting apoptosis-specific DNA fragmentation, it is demonstrated that proximal tubular cells (LLC-PK(1)) and medullary interstitial cells (RMIC) respond with programmed cell death when treated with therapeutic doses of AmB. Concomitant application of AmB and recombinant human insulin-like growth factor-1 (rhIGF-1), a known antiapoptotic agent, abrogated apoptosis in vitro. To validate that the observed apoptotic effects on renal tissue culture cells are applicable to an in vivo setting, an animal model was used for verification. Therefore, Sprague-Dawley rats were treated with AmB. The drug caused hypokalemia, decreased weight gain, loss of renal concentrating ability, and dehydration in a dose-dependent fashion. Microscopic examination of renal tissue sections revealed apoptotic alterations predominantly in proximal and distal tubular epithelial cells. To verify that the observed clinical side effects were linked to apoptosis, rhIGF-1 was applied concomitantly with AmB. In all animals, rhIGF-1 prevented the above-mentioned clinical side effects. Moreover, significantly reduced apoptosis was observed in renal tissue sections of these animals, indicating the relevance of apoptosis in nephrotoxicity. This is the first report to demonstrate that AmB induces apoptosis in the rat kidney in a dose-dependent fashion. The incidence of apoptosis correlates with renal toxicity and can be abrogated by concomitant treatment with rhIGF-1.

Early sonographic aspects of kidney morphology in Bardet-Biedl syndrome.

Bardet-Biedl syndrome is an autosomal recessive disorder characterized by postaxial hexadactyly, obesity, mental retardation, pigmented retinopathy, hypogonadism, and renal disease. Morphological changes are present in all areas of the kidney, the renal medulla being the most frequently affected site. Cystic and dysplastic changes are prevalent. Seven children from five families were followed from birth through their 5th birthday. Serial renal sonography revealed a number of characteristic features. Bilateral renal enlargement and increased parenchymal echogenicity were present at birth. The usual corticomedullary differentiation was absent. Pyramids were either not seen or deformed. With high-resolution ultrasonography, small cysts were detected at the corticomedullary junction. After the 3rd month of life, there was a striking inversion of normal echogenicity, the inner medulla became more echogenic and was demarcated from the less-echogenic cortex. After 12 months, the kidney size regressed significantly. Fetal lobulation persisted in some patients. In conclusion, ultrasonography is a useful tool to evaluate the extent of renal lesions, but more importantly to differentiate bilateral polycystic kidney diseases in the newborn period.

Non-neurogenic bladder and chronic renal insufficiency in childhood.

Functional voiding disorders and urinary tract infections are common in childhood, but are usually not accompanied by upper urinary tract deterioration. Nevertheless a small group of children remain at risk of developing chronic renal insufficiency (CRI). Clinically these children present day and night wetting. The most important parameter, however, is urinary retention which is reflected by an abnormal voiding pattern in the uroflow curve. After ruling out patients with neurogenic or anatomical disorders, nine girls with psychogenic urine retention were observed for 5 years. Terminal renal insufficiency was seen in one, CRI in five patients and in three patients the kidney function could be maintained, but they all had severe scarring of at least one kidney. Furthermore, all revealed a dilation of the bladder and the upper urinary tract. Vesicoureteral reflux occurred in six and obstruction of the ureterovesical junction in three patients. Two girls underwent repeated reflux surgery resulting in a rapid deterioration of renal function. Three patients developed hypertension and one had a hypertensive crisis with microangiopathic anaemia and acute renal failure. Psychogenic disorders and problematic family settings were observed in all cases. Bladder training, transitory suprapubic catheters, intermittent catheterisation, medication and psychotherapy can avoid severe kidney damage and achieve a stabilisation of renal function. It is important to bear this syndrome in mind when evaluating girls with asymptomatic bacteriuria and urinary retention.