Ureteral obstruction is an infrequent complication after renal transplantation that may cause rapid loss of transplant function. We tested static fluid MR urography for determining the cause of graft hydronephrosis. Magnetic resonance urography was performed in nine transplants with dilated collecting systems on ultrasound. A heavily T2-weighted 3D turbo spin-echo sequence on a 1.5-T scanner was used and maximum intensity projections were obtained. The patients also underwent excretory urography (n = 1), renal scintigraphy (n = 1), antegrade pyelography (n = 3), voiding cystourethrography (n = 4), and non-enhanced CT (n = 2). Six patients had pathologic conditions including ureteral stricture, compression by lymphoceles, implantation stenosis, vesicoureteral reflux, and late-occurring transitional cell carcinoma at the implantation site. Static MRU was able to diagnose or exclude a dilation of the graft collecting system. It visualized the course of the ureters and localized the obstruction site in four of five obstructed transplants. In one case the ureter was obscured by lymphoceles, which were demonstrated by hydrographic MRU as well. The definite cause for obstruction was provided in only 2 of 5 cases. Dilation due to vesicoureteral reflux could not be differentiated. The current multimodality approach to renal transplant imaging already provides comprehensive assessment of graft hydronephrosis. Static MRU may be useful in some cases since complications associated with intravenous iodinated contrast or antegrade pyelography can be avoided. Its main drawback, the lack of functional information, may be overcome by combining it with contrast-enhanced MRU.

This paper is the third of a long-term planned series of papers dealing with ex vivo investigations of drug transport in human kidney. The aims of this study are (a) to investigate whether or not human renal cell carcinoma (RCC) can actively accumulate p-aminohippurate (PAH) and (b) to test the response of RCC on dexamethasone or triiodothyronine (T3) using tissue slices ex vivo. By this approach, the accumulation capacity of RCC should be stimulated as a prerequisite for an increased uptake of anti-tumour drugs. Tissue slices of RCC samples of 30 patients were incubated for 24 h in Williams medium E containing 0.01-50 microM dexamethasone or T3. Thereafter, slices were placed in PAH-containing Cross-Taggart medium, and PAH uptake into kidney tissue was measured for 2h under standardised conditions as described previously. In intact human renal cortical slices, PAH uptake capacity, expressed as slice to medium ratio (QS/M), was about 2.8 +/- 0.16 after 24 h of incubation and increased significantly in dexamethasone-containing medium in a concentration-dependent manner, up to approximately 150%, whereas T3 did not influence PAH accumulation. On the other hand, in RCC the PAH accumulation capacity was completely abolished (QsM approximately 1). However, after administration of dexamethasone, the accumulated amount of PAH increased significantly in RCC tissue in a concentration-dependent manner, up to approximately 190%. T3 was without effect in RCC, too. Surprisingly, the dexamethasone-mediated stimulation could be differentiated into responders and non-responders, with maximal effects at different concentrations for each patient. Nevertheless, the maximal transport rates remained low in RCC, even under hormone influence. In conclusion, a moderate stimulation of tubular transport capacity can be shown ex vivo in human RCC. This phenomenon is only of a relatively low degree compared with intact renal tissue. However, in principle, the response of RCC on dexamethasone could form a basis for further therapeutic strategies to overcome multi-drug resistance in RCC patients. For this purpose, additional experiments analysing the expression of transporters of the ABC cassette-type are in progress.

The aim of this study was to test whether or not the accumulation of p-aminohippurate (PAH) can be increased in intact human renal cortical slices obtained from tumor-bearing kidneys of patients suffering from renal cell carcinoma (RCC). Tissue slices were incubated for 24 h in Williams medium E containing 0.01-50 microM dexamethasone. Thereafter slices were placed in PAH-containing Cross-Taggart medium and PAH uptake into kidney tissue was measured for 2 h. In both rat and human renal tissue slices, PAH uptake capacity increased significantly in a concentration-dependent manner after 24 h of incubation in dexamethasone-containing medium (rat, 136%; man, 156%). The stimulatory effect was already significant after 12 h of incubation. In additional experiments it was shown that incubation in triiodothyronine (T3)-containing medium has different effects: in man, T3 does not influence the PAH accumulation capacity of renal cortical slices whereas in rats PAH accumulation is significantly lower after 24 h of incubation with T3. Thus stimulation of tubular transport capacity can be performed in vitro in human renal cortical slices. Discrepancies between the effects of dexamethasone and T3 indicate different modes of action of the two hormones at the cellular level.

In vitro accumulation of p-aminohippurate (PAH) was investigated in "intact" human renal cortical slices of normal kidney tissue and in tissue slices of renal cell carcinoma (RCC). The technique used was established in preliminary experiments on rat kidney tissue slices. In principle, the accumulation capacity is comparable in renal tissue slices of both species (slice to medium accumulation ratios between 4 and 8). In man sex differences in accumulation capacity do not exist. But, as shown in detail for rats, accumulation capacity drops with age. Tissue slices of RCC are unable to accumulate PAH actively; slice to medium ratio reaches about 1 and indicates passive PAH uptake only. Surprisingly, in tumors of stage pT1 PAH uptake is lowest. perhaps as a sign of PAH transport out of the cells. There is no difference between peripheral and central parts of RCC. Age and sex are without influence on PAH uptake in RCC tissue slices. Interestingly, the accumulation capacity of "intact" tissue of kidneys infested with RCC also depends on the severity of the tumor (stage, diameter), but not on grading and formation of metastases.