Reproducibility of Doppler ultrasound measurement of resistance index in renal allografts.

In recent years measurements of arterial blood flow in the renal allograft have been studied in an attempt to provide a non-invasive method of diagnosing and monitoring post-transplant renal dysfunction. Many studies have involved measurement of the resistance index (RI) of arterial blood flow. Although the reproducibility of the technique has been studied in other areas of application, no such studies have been performed on the renal allograft. In this study we attempted to evaluate the reproducibility of the measurement of the RI of the interlobar artery in the renal allograft. 18 renal allograft recipients with stable functioning grafts were studied twice by each of two experienced sonographers using a colour-coded duplex Doppler ultrasound scanner, in order to determine the intraobserver and interobserver variability in the measurement of RI of the interlobar arteries in the allograft. Variability was small and although interobserver variability exceeded intraobserver variability, both were within repeatability limits adopted by the British Standards Institution. The results suggest that measurement of the RI of the interlobar artery of renal allografts is repeatable and reproducible when performed by experienced operators.

The reflush effect--a prospective analysis of late perfusion.

This prospective randomized trial examines the effect of a "reflush" with preservation solution immediately prior to renal allograft implantation, using hyperosmolar citrate (HOC, n = 10) or phosphate-buffered sucrose (PBS140, n = 10) versus no reflush (n = 10). All kidneys had been stored in HOC. The HOC reflush did not alter the postpreservation intra- or extracellular electrolyte milieu, whereas the PBS140 reflush resulted in an apparent overall loss of both sodium and potassium from the kidney (P < 0.0005). A small amount of calcium was released into the venous effluent in both reflush groups. A similar amount of lactic acid was released into the venous effluent of the two reflush groups, reflected by a lower pH (P < 0.0005), and there was a similar loss of lactate dehydrogenase and creatine phosphokinase. An analysis of procoagulant activity in the first urine produced was performed as a marker of reperfusion injury. The median value was higher in the No Reflush group at 457.5 units, compared with 263.0 and 209.0 units for the PBS140 and HOC Reflush groups, respectively (P = 0.06). Reflushing the kidneys reduced the postoperative dialysis requirement (from 40% to 15%), but by the end of the first posttransplant week there was no significant difference between the renal functional analyses of the three groups, and there was no difference at one year. The proposed mechanism for the early renal functional improvement is a reduction in the calcium paradox and free radical formation, by release of calcium and ATP breakdown products into the venous effluent prior to implantation.

Cisplatin-resistant metastatic hepatoblastoma: complete response to carboplatin, etoposide, and liver transplantation.

A child with stage 4 hepatoblastoma failed to respond to treatment with cisplatin and adriamycin. She then showed a response to carboplatin with complete clearing of pulmonary metastases. Bilobar liver disease persisted, although significantly reduced in size. A liver transplant was subsequently performed and she remains in complete remission 36 months later. After the first course of carboplatin, there was a dramatic rise in alpha-feto protein which then fell exponentially. Carboplatin warrants further study in hepatoblastoma.

Monitoring renal allograft rejection with duplex sonography.

Thirty-six renal allograft recipients were monitored by serial duplex Doppler ultrasound studies post-transplant and during early rejection. A separate reproducibility study demonstrated no significant inter- or intra-operator variability in measurements of resistive index of an interlobar artery (RI) (2.1% [1.5%] and 3.2% [2.3%] respectively, mean [standard error] of coefficients of variance). Twenty-one patients had rejection within 3 weeks of transplantation. These grafts showed greater overall rises in the RI, from day 2 to day 5 post-transplant, than the grafts which had no rejection. Eleven of the 21 patients required more than one course of methyl-prednisolone for persistent or recurring rejection. These grafts had higher RI on the day rejection was diagnosed (81 [7.3], median [interquartile range]) compared with the remaining 10 patients (68.6 [8.7]). The 11 grafts with persistent rejection had higher RI (p less than 0.005, Mann-Whitney U-test) on day 2 post-transplant (76 [3.9]) compared with the 10 grafts successfully treated with a single course of methyl-prednisolone (63.2 [10.9]). This study demonstrates that grafts with an RI of greater than 70 on day 2 post-transplant are likely to have rejection requiring additional treatment (sensitivity--100%, specificity--80%). These patients may be candidates for earlier or alternative anti-rejection therapy.

Ureteric complications of renal transplantation.

Of 507 consecutive recipients of renal allografts, 45 developed a urological complication. In 39 patients (7.7%) ureteric problems were implicated and these comprised 30 cases of obstruction and 9 cases of ureteric necrosis presenting as urinary leakage. In 7 patients ureteric obstruction resolved following a period of nephrostomy decompression; 10 patients were reconstructed surgically and this was successful in 8, with 2 patients requiring further surgical procedures. Ten patients were successfully treated by percutaneous stenting after dilatation of the stricture. Stenting failed in 4 patients and in 1 patient caused rupture of a calix. All 10 stents have now been removed and there is no recurrence of stricture (follow-up 32.0 +/- 8.6 months). Of the remaining 3 grafts, 2 were removed and the other graft had percutaneous removal of a ureteric calculus. The 1-year survival rate of allografts in the ureteric complication group was 84.6%; in the recipients without a urological complication it was 81%. It was concluded that an active approach to ureteric problems following renal transplantation results in the rescue of the majority of allografts.

Role of duplex imaging and fine needle aspiration cytology of renal allografts in monitoring response to anti-rejection therapy.

The role of duplex imaging and fine-needle aspiration cytology (FNAC) in monitoring the response to anti-rejection therapy was investigated in 14 of the 22 rejection episodes which occurred in 30 renal allografts recipients. In 9 of these 14 episodes of rejection, with good resolution, both resistive (RI) and pulsatility (PI) indices decreased by significant proportions (p less than 0.05). The FNAC scores also fell significantly with anti-rejection therapy. In 5 other episodes of rejection where the graft continued to deteriorate there was no significant fall of RI and PI (p greater than or equal to 0.2). In a small group of patients, both FNAC and Doppler predicted rejection. In conclusion, both duplex imaging and FNAC have a role in selection and optimal modulation of drugs in the treatment of acute renal allograft rejection.

Early computed colour echo Doppler imaging following renal transplantation.

Thirty patients with renal allografts were monitored for 15 postoperative days by colour-coded Doppler imaging and categorized as stable, rejection, acute tubular necrosis and cyclosporine toxicity. All forms of graft dysfunction showed significantly raised resistance (P less than 0.01) and pulsatility (P less than 0.01) indices (RI and PI, respectively). It was not possible to use Doppler imaging to differentiate the cause of graft dysfunction, but stable grafts in patients with high cyclosporin levels had significantly higher RI (P less than 0.04) and PI (P less than 0.04) than similar grafts in patients with cyclosporine levels in the therapeutic range.

Improved porcine renal preservation with a simple extracellular solution--PBS140.

In this prospective randomized trial a porcine model of renal autotransplantation was used to compare quality of preservation, as reflected by detailed analysis of posttransplant renal function, following 24-hr cold storage in phosphate-buffered sucrose (PBS140), hyperosmolar citrate (HOC), and University of Wisconsin (UW) preservation solutions. There were 6 deaths with primary nonfunction: 3 of 5 HOC, 2 of 5 UW, but only 1 of 5 PBS140. Analysis of the whole group and separate analysis of the survivors demonstrated significantly better renal function following preservation with PBS140 when compared with both HOC and UW, with a lower peak serum creatinine (P = 0.02) and improved loop of Henle function (P = 0.02). The animals in the PBS140 group also demonstrated a more rapid return to normal creatinine, higher GFR, improved tubular function, and higher effective renal plasma flow, with figures approaching statistical significance (P = 0.06-0.07). The proposal of UW as a universal storage medium prompted this study, and its results suggest the need for a clinical comparison of renal preservation using UW and PBS140 in a prospective randomized trial.

Ultrasonography of renal allografts: collecting system dilatation and its clinical significance.

Reports and ultrasound scans (658 studies) of 135 renal allografts, transplanted in the years 1987 and 1988, have been reviewed. Records of the recipients were also studied in order to determine the clinical status of the kidney at the time of each ultrasound examination and to obtain long-term follow-up of allograft function. Seventy-seven allografts (57%) never showed pelvicalyceal dilatation on 342 serial examinations. Forty-two kidneys (31%) had mild dilatation reported on at least one scan, which did not progress. However, 11 mildly dilated allografts developed moderate to severe dilatation on later examinations and these, together with 5 allografts reported as exhibiting moderate to severe hydronephrosis on their first dilated scan, were classed as moderate to severe (n = 16 = 12%). Thirty-eight patients (90%) with mild dilatation of the collecting system had no evidence of obstruction. However, in allografts with moderate to severe dilatation and poor or deteriorating function, ten patients (70%) were found to have ureteric obstruction. There was no significant difference in 1-year graft survival (87% versus 81.8%) and the median serum creatinine at 3 and 12 months after transplantation between non obstructed 'dilated' and non-dilated allografts (149 mumol/l versus 153.7 mumol/l; 139 mumol/l versus 147.3 mumol/l). All 14 obstructed allografts were salvaged with a graft survival of 85.7% at 1 year. Median serum creatine in these patients was significantly elevated at 200 mumol/l and 189 mumol/l at 3 and 12 months; P = 0.05 and 0.01 compared to dilated non-obstructed allografts. Our results indicate that grafts with moderate to severe dilatation should be urgently investigated to minimise further allograft damage.

Ranolazine--a new drug with beneficial effects on renal preservation.

Ranolazine is a new drug with a novel mode of action as a metabolic modulator and membrane stabilizer. In this prospective randomized double-blind trial, a porcine model of renal autotransplantation was used to assess the effects of this drug during preservation and reperfusion of kidneys cold-stored for 24 hr in phosphate-buffered sucrose (PBS140). Three groups of 10 animals were compared: a Placebo group (placebo given intravenously to the animal before nephrectomy, added to the preservation solution, and given again to the animal during reperfusion); a Storage group (Ranolazine before and during storage, placebo during reperfusion); and a Reperfusion group (placebo before and during storage, Ranolazine during reperfusion). Detailed analysis of posttransplant renal function was carried out over a 14-day follow-up period. There were 7 deaths with primary nonfunction: 2 Placebo, 1 Storage, 4 Reperfusion. Analysis of the whole group and separate analysis of the survivors demonstrated significantly improved glomerular (P less than 0.05), tubular (P less than 0.05), and loop of Henle (P less than 0.05) function in the Storage group. The results of this study clearly demonstrate the beneficial effects of Ranolazine during the storage phase of porcine renal preservation, and further investigation of this drug is warranted.

Treatment of metastatic Vipoma by liver transplantation.

We report the first case of metastatic Vipoma treated by orthotopic liver transplantation. A woman with explosive secretory diarrhea causing hypokalemic acidosis was diagnosed as having a vasoactive intestinal peptide secreting tumor with widespread hepatic metastases. The symptoms were initially controlled for 9 months with increasing doses of long-acting somatostatin analogue (Sandostatin, Sandoz Ltd, UK). Alpha interferon was not tolerated, causing an acute paranoid psychosis. Eventually orthotopic liver transplantation was performed with the removal of the primary tumor from the distal pancreas. Postoperatively, complications were associated with the distal pancreatectomy. The patient has no evidence of tumor recurrence on imaging or serum VIP level 12 months posttransplantation.

Does the Warren shunt correct hypersplenism?

It has been suggested that patients with bleeding varices and hypersplenism will show significant improvements in leucocyte and platelet counts following distal splenorenal (Warren) shunt surgery. Whilst this may be true in the short term, this report shows that in the long term hypersplenism is not relieved, whereas the lienorenal shunt is associated with a return of normal haematological values.

Urinary aluminium excretion following renal transplantation and the effect of pulse steroid therapy.

Urinary aluminium was measured in 48 patients with primary graft function for 14 days following renal transplantation. The plasma aluminium prior to transplantation was greater in those prescribed aluminium-containing phosphate binders (1.7 +/- 0.2 vs 0.6 +/- 0.2 mumol/L, P less than 0.05) and correlated with the duration of dialysis therapy (r = 0.42, P less than 0.008). After an initial reduction the plasma aluminium returned to pre-transplant values by the fifth day. The 24 h urinary aluminium excretion, aluminium clearance and fractional aluminium excretion all increased during the first week to a maximum around the sixth postoperative day, thereafter returning to values obtained during the first postoperative days, suggesting an early 'wash-out' of a readily accessible aluminium pool followed by a lower steady state determined by the rate of release of aluminium from tissue stores. For the whole group, aluminium excretion, at this steady state, was five times that of urinary aluminium excretion in normal subjects. Acute allograft rejection was diagnosed in 25 patients, who were treated with pulsed methyl prednisolone. Apart from improving graft function, no additional effect was observed on aluminium excretion, suggesting that the readily accessible aluminium pool does not come from lysosomal release, but probably from aluminium bound to small molecular weight protein.

Interaction of intravenous methylprednisolone with oral cyclosporin.

The plasma cyclosporin values during 17 consecutive rejection episodes in 13 renal allograft recipients have been monitored by high-performance liquid chromatography and radioimmunoassay. In response to anti-rejection therapy with intravenous methylprednisolone, there was a significant increase of greater than 100 ng/ml on only three occasions. We suggest that elevated cyclosporin values during rejection episodes should not be dismissed as the result of steroid therapy and that the original diagnosis must be reviewed.

Recurrent pyogenic cholangiohepatitis.

Three cases of complicated oriental cholangiohepatitis are described in patients of Asian origin. The development of high biliary strictures in two patients required liver resection; in the third patient the process was complicated by a presumed bile duct malignancy. Oriental cholangiohepatitis may be expected in UK surgical practice given the increased frequency of migration from Asia.