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Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3–30.2%] in kidney transplant and 25.0% (95% CI 20.2–30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59–1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

Objective Several adjustments occur after nephrectomy (NT) in the donor's remnant kidney. We investigated kidney donors 10 years after NT and compared several parameters before and after transplantation. Methods A total of 42 kidney donors of the University of Luebeck's Transplant Center were scheduled for a 10-year follow-up and were offered several investigations: laboratory tests, urinalysis and kidney ultrasound examination including determination of kidney volume (KV), resistive index (RI) and pulsatility index (PI). Moreover, a 24-hour ambulatory blood pressure monitoring (ABPM) was performed. A review of the medical records allowed comparison of the investigated parameters before (t0), 1 month after (t0.1), and 10 (t10) years after NT. Results Creatinine clearance decreased from 94.3 ± 23 (t0) to 52.4 ± 22 mL/min/1.73 m2 (t0.1) and increased to 78.2 ± 19 mL/min/1.73 m2 after 10 years (t10). Tubular proteinuria (α1-microglobuline) increased from 6.1 ± 1.5 (t0) to 63 ± 4.8 (t0.1) (P Conclusions NT leads to hypertrophy of the remnant kidney associated with an increase of organ volume and creatinine clearance after 10 years of follow-up. Our results indicate an excellent prognosis for the kidney donors without any signs of renal damage.

Objectives Renal duplex sonography represents a standard noninvasive diagnostic procedure to demonstrate morphologic changes in acute kidney transplant dysfunction. We investigated whether a newly developed serial duplex index (SDI) can differentiate between acute cellular rejection and acute vascular rejection more effectively than the established Doppler parameters of the resistive index (RI) and pulsatility index (PI) in recently transplanted patients. Methods Serial duplex scans of patients with histologically proven acute tubular necrosis (n = 25), acute cellular rejection (n = 28), acute vascular rejection (n = 18), and normal graft function (n = 50, partially protocol biopsied) were retrospectively analyzed. For each patient, the RI, PI, and cortex-pelvis proportion (CPP) were included from the day of biopsy (t0) and 3 to 7 days before biopsy (t–1). The sequential CPP ratio (CPPt0/CPPt–1), RI ratio (RIt0/RIt–1), and PI ratio (PIt0/Pit–1) were determined. The SDI was calculated as: RI ratio × PI ratio/CPP ratio. The diagnostic accuracy of the SDI was compared with that of the RI and PI ratios. Results Selected groups were statistically comparable in all routinely determined transplant parameters. The SDI was significantly different between patients with normal graft function, acute cellular rejection, and acute vascular rejection (P

The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy-proven acute rejection in the low-dose tacrolimus group was approximately half that of the standard-dose cyclosporine and low-dose cyclosporine groups, and a third of that in the low-dose sirolimus group. The low-dose cyclosporine group had more severe rejection episodes (≥grade II) compared with other groups. Acute rejection was associated with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute increase in graft loss at 12 months. Overall, the highest GFR was found in both rejecters and non-rejecters receiving low-dose tacrolimus, both in an intent-to-treat analysis and in patients successfully treated according to the protocol. In Cox regression models, human leukocyte antigen (HLA) mismatches and expanded criteria donors increased the acute rejection risk, while recipient age, living related donor, and MMF dose were associated with a reduced risk. Acute rejection was associated with worse outcome but did not entirely explain the differences among the treatment groups. The 2 g MMF plus low-dose tacrolimus combination appears to be the most efficient of all regimens examined regardless of acute rejection.

BASIC PROBLEM AND OBJECTIVE Viral, especially cytomegalovirus (CMV), infections are after rejection reaction the most serious problem following organ transplantation. The risk of disease correlates with the CMV donor/recipient constellation and the degree of immunosuppression. The importance of antiviral prophylaxis remains unresolved. Whether drug prophylaxis adapted to the individual risk is of clinical value was investigated in a prospective study. PATIENTS AND METHODS A risk-adapted stepwise antiviral prophylactic regimen was given to 62 patients with renal transplants. All patients at risk of CMV infection were given acyclovir, 200 mg four times daily for 3 months. Patients with rejection reaction for which they were receiving i.v. immunosuppressive treatment additionally received CMV hyperimmunoglobulin (2 ml/kg body weight on days 1 and 14). High-risk patients (donor CMV positive and recipient CMV negative) were given as basic prophylaxis CMV hyperimmunoglobulin i.v. on days 1 and 14 after transplantation, and additionally i.v. ganciclovir during any rejection treatment. The results were compared with those of a retrospectively selected patient cohort (n = 52) who had received only acyclovir as basic prophylaxis. The diagnosis of CMV infection was made by demonstrating CMVpp65 antigen in blood. In the prospectively studied patients measurement of beta 2 microglobulin concentration was used to determine viruria in 24-hour urine. RESULTS Among the high-risk group (donor CMV positive/recipient CMV negative) the additional prophylactic regimen significantly reduced the proportion of CMV-associated cases of rejection (14% compared with 42%, P < 0.05) in the basic prophylaxis only group. Similar results were obtained for CMV-caused transplant loss within the first 3 years (19% vs 50%, P < 0.05). The additional prophylaxis had no influence on the incidence of CMV infection. In case of active infection an isolated rise of beta 2-microglobulin in urine occurred in active infection at a mean of 6 days before CMVpp65 antigenaemia (sensitivity of 89%). CONCLUSIONS These results indicate that risk-adapted antiviral prophylaxis can decisively influence the long-term prognosis for a renal transplant, but not the incidence of CMV infection. The early and reliable diagnosis of active CMV infection is made possible by the combined use of beta 2-microglobulinuria and pp65 antigenaemia.

A prospective study was undertaken in 73 patients (24 women, 49 men; mean age 47.9 [21-64] years) after renal transplantation to discover whether the presence of C-reactive protein in urine (CRPu) and its serum concentration (CRPs) are of value in the differential diagnosis of abnormal function in the transplanted kidney. CRPu concentration was measured with a highly sensitive immunoluminometric assay (minimal threshold value 6 micrograms/l). CRPu was demonstrated in 36 histologically proven rejection episodes and 21 bacterial infections proven by culture. In contrast, no CRPu was demonstrated when the course was normal and in individual cases of cyclosporin renal toxicity, as well as in 27 of 34 cases of cytomegalovirus infection. In addition, the CRPs to CRPu ratio was a sensitive means of distinguishing between rejection (CRPs/CRPu less than 1) and bacterial infection (CRPs/CRPu greater than 1). Determining CRPu concentration thus proved to be useful in the initial monitoring of renal transplantation before starting any specific urinary protein diagnosis, as well as (together with CRPs) in the diagnosis of severe posttransplantation complications.

In a prospective study the occurrence of cytomegalovirus (CMV) infection was diagnosed by demonstrating CMV-immediate early antigen (IEA) in the blood in 13 out of 68 (19%) patients who had undergone renal transplantation (27 women, 41 men, mean age 46.3 [21-64] years). Twenty-four hour urine samples were collected at the same time for quantitative determination of selected marker proteins by immunoluminometric assays (IgG and transferrin as glomerular markers, alpha 1-microglobulin and beta 2-microglobulin as tubular markers). In all 13 confirmed cases of CMV infection there was an isolated rise in urinary beta 2-microglobulin excretion amounting to more than three times the normal. In 11 of the 13 cases the beta 2-microglobulinuria was noted before the CMV-IEA test became positive. This suggests that quantitative assay of beta 2-microglobulin in the urine may be of value in the early diagnosis of CMV infection--a matter of some prognostic importance--and may hence offer additional support for therapeutic decisions.

BACKGROUND AND OBJECTIVE After renal transplantation hypertension occurs in 60-80% of patients, in 3-23% of them due to renal artery stenosis in the transplanted kidney. Angiographic assessment of the severity of the stenosis would best be done with a non-nephrotoxic contrast medium. We investigated the use of carbon dioxide, a bubble-forming contrast medium excreted via the lung, for its suitability in the angiography of the arterial system in the renal transplant. PATIENTS AND METHODS In an uncontrolled series of observations on six patients with renal transplants and hypertension who were being treated with three or four antihypertensive drugs, the transplant's arteries were demonstrated with carbon dioxide, injected by Seldinger technique into the ipsilateral femoral artery, and the results recorded by subtraction angiography. RESULTS The angiograms demonstrated postoperative kinked renal artery, a plaque in the external iliac artery, and a sharply angled origin of the external iliac artery in one case each, and three normal cases. CONCLUSIONS Carbon dioxide is a suitable medium for demonstrating renal arteries in a transplanted kidney and is preferable to conventional contrast media for the angiographic diagnosis of possible renal artery stenosis.

The interleukin-6 -174promoter polymorphism is associated with long-term kidney allograft survival.BackgroundTh1-dependent effector mechanisms may be responsible for allograft rejection. Recently, interleukin-6 (IL-6) has been shown to antagonize CD4+ T cells to effector Th2 cells and, in the process, differentiate them into Th1 cells.MethodsTo assess the role of IL-6 in long-term allograft survival, 158 patients after first cadaveric kidney transplantation were analyzed for the biallelic –174G→C promoter polymorphism of the IL-6 gene.ResultsCarriers of the –174C-allele (genotype GC/CC) had an inferior three-year graft survival (71/104 = 68.3%; P = 0.0059) with a 3.7-fold increased relative risk of graft loss compared to carriers of the –174GG-genotype (48/54 = 88.9%). The –174GC/CC-genotype retained its negative impact on graft survival when other established prognostic factors and further cytokine polymorphisms (-308TNF-α, TGF-β1 codon 10 & 25, -592/-819/-1082IL-10 and +874IFN-γ) were considered simultaneously.ConclusionsSince the clinical impact on transplant outcome seems as important as matching for histocompatibility antigens, genotyping of the IL-6 -174polymorphism may offer a new method for identifying patients at increased risk of allograft loss.

Background A double-blind, placebo-controlled, randomized study was performed to assess whether immunoprophylaxis with basiliximab (Simulect) could reduce the incidence of acute rejection in kidney transplant recipients treated with cyclosporine (Neoral), steroids, and azathioprine. Methods Three hundred forty patients received either placebo or basiliximab at a dose of 20 mg, given intravenously on days 0 and 4. All patients received cyclosporine, steroids, and azathioprine. The primary endpoint was the incidence of acute rejection at 6 months. Secondary endpoints included the safety and tolerability of basiliximab and placebo, 1-year patient and graft survival, and significant medical events up to 12 months. Results During the first 6 months posttransplantation, acute rejection occurred in 20.8% of patients given basiliximab versus 34.9% of patients administered placebo (P=0.005). Similarly, there was a reduction in biopsy-proven acute rejection at 6 months in the patients receiving basiliximab (P=0.023). One-year patient survival was 97.6% with basiliximab and 97.1% with placebo, graft survival was 91.5% versus 88.4%, respectively (NS). The adverse-events profile of patients treated with basiliximab was indistinguishable from that of patients treated with placebo. The number of patients with infections was similar (65.5% for basiliximab vs. 65.7% for placebo), including cytomegalovirus infections (17.3% vs. 14.5%, P=0.245). Nine neoplasms (three in the basiliximab group, six in the placebo arm) were recorded up to 1 year from transplantation. Conclusions Basiliximab in combination with cyclosporine, steroids, and azathioprine triple therapy was highly effective in reducing the incidence of acute renal allograft rejection without increasing the incidence of infections and other side effects.

Background. The acute immunological rejection and long time survival of kidney allografts are correlated with the human leukocyte antigen (HLA) match status between donor and recipient. HLA-A, -B and -DR have all turned out to be relevant HLA loci in several studies. The role of HLA-C has: not been studied before now. Methods. In 104 consecutive patient:donor pairs from our transplantation unit, we retrospectively analysed whether acute graft rejection is influenced by HLA-C match status between donor and recipient. For typing HLA-C alleles. we used an allele-specific PCR protocol in combination with serology. Results. By analysing groups of donor/recipient pairs with a homogenous distribution of HLA-B mismatches inn order to exclude an effect of the linkage disequilibrium between HLA-B/C, HLA-C mismatch turned out to be significantly correlated with acute transplant rejection in pairs with one additional mismatch on the B locus (P = 0.004). Additional parameters that may hypothetically influence acute rejection episodes (HLA-A or DR mismatch, time of cold and warm ischaemia, previous transplantations, pre-existing HLA antibodies) were also analysed but cannot explain this finding. Conclusion. HLA-C matching of all kidney donors and recipients seems to be an option to reduce the probability of acute rejection episodes. Further studies of greater patient cohorts analysing organ rejection and organ survival are warranted.

While the relevance of pre-formed anti-human leukocyte antigen (HLA) antibodies has been studied extensively, the role of anti-HLA class I and II antibodies produced after cadaveric kidney transplantation is still a matter of discussion. As it has been proposed that they are involved in a considerable number of cases, it should be investigated whether a post-transplant monitoring is a sensitive parameter for the early diagnosis of acute rejection episodes. Additionally, it has been suggested that antibodies are a major cause for chronic rejection; thus, it would be of interest to correlate antibody detection and graft survival. We retrospectively investigated 59 patients after a first cadaveric kidney transplantation without known anti-HLA antibodies (complement-dependent cytotoxicity [CDC] testing). The panel reactivity was determined with a new highly sensitive and specific flow-cytometric technique (Flow-PRA Screening Test, One Lambda, Canoga Park, USA) in sequentially collected serum samples pre- and post-transplant. In patients with acute rejection episodes during the clinical course, the last sample prior to rejection, and in patients without rejection, the last sample prior to discharge, was analyzed. Furthermore, we analyzed 3-yr graft survival and several clinical parameters such as cold ischemia time (CIT). Twenty-four of 59 patients (41%) experienced acute rejections during the clinical course. Five of 59 died with a functioning graft within the first 3 yr. Seven of 54 patients, still alive after 3 yr, lost their graft. Anti-HLA antibodies were detectable in only 7/59 patients and a correlation between antibody positivity and acute rejections (p = 0.32 and 0.54 for anti-HLA class I and II, respectively) could not be identified (sensitivity 12.5 and 8.3%). However, we found a significant correlation between the detection of anti-HLA class II and graft loss within 3 yr (p = 0.005, specificity 97.9%). Additionally, anti-HLA class II positive patients had significantly longer CIT (p = 0.003). Whether the detection of anti-HLA class II antibodies in the early post-transplant phase is of great value for the identification of patients at high risk for early graft loss needs additional investigation. However, we found that anti-HLA antibodies are detectable only in a minority of unsensitized patients and we conclude that flow-cytometric monitoring with Flow PRA is not a sensitive parameter for the early diagnosis of acute rejection episodes in patients after first cadaveric kidney transplantation.

To evaluate the use of laparoscopic techniques in patients with a renal transplant.Since 1992, 358 patients have undergone urologic laparoscopy at our hospital. Among these, 37 procedures (10.4%) were performed in patients with a renal transplant: 14 bilateral nephrectomies for severe drug-resistant hypertension, 9 marsupializations of symptomatic lymphoceles, 6 renal allograft biopsies in patients with clotting abnormalities, 6 unilateral nephrectomies, and 2 nephroureterectomies for recurrent episodes of pyelonephritis and symptomatic vesicoureteral reflux, respectively.Five complications (14%) and three conversions (8%) occurred. Patients who underwent successful laparoscopic operations began mobilization and oral intake on the day after the operation. The hospital stay ranged from 1 to 6 days. In the nephrectomy groups, perioperative urine outputs remained stable and post-operative urine outputs were increased as compared with those in the perioperative period (P0.05). Post-operatively, serum creatinine remained stable or improved in patients who underwent nephrectomy or marsupialization of lymphocele.Our results indicate that laparoscopic techniques are safe and effective in the treatment of patients with a renal transplant. Renal allograft function apparently is not affected by laparoscopic procedures.

We report our experience with bilateral laparoscopic nephrectomy after renal transplantation.Between August 1994 and October 1995, 11 patients who had previously undergone renal transplantation underwent bilateral laparoscopic nephrectomy at our hospital due to poorly controlled hypertension. The records of 10 patients undergoing bilateral open nephrectomy were reviewed for comparison.Mean operative time in the laparoscopy group was 195 minutes (range 125 to 270). Mean blood loss was 345 ml. and 1 patient required conversion to an open operation. Oral intake and mobilization were begun 1 day postoperatively. Mean postoperative morphine equivalent consumption was 14 mg., mean hospital stay was 4.2 days (range 3 to 6) and mean return to normal activities was 14 days. At a mean followup of 10.4 months blood pressure had improved significantly in 8 patients (73%). Mean operative time in the open surgery group was 145 minutes (range 115 to 170) and mean postoperative morphine equivalent required was 44 mg. Compared to the laparoscopy group the interval to resumption of oral intake (3.5 days), duration of hospital stay (10.7 days) and return to normal activities (36 days) were prolonged in the open surgery group.According to our results, bilateral laparoscopic nephrectomy could be an effective alternative for the treatment of severe hypertension after renal transplantation. Compared to open nephrectomy most patients benefit from the laparoscopic approach.

A 58-year-old woman presented with hemolysis and thrombocytopenia 2 weeks after receiving a kidney graft. Hemolytic uremic syndrome was initially suspected, because in addition to hematological changes the graft function was missing. Unexpectedly, the results of the direct antiglobulin test became positive (4+), which is not normally observed in the hemolytic uremic syndrome. Differentiation of the eluted antibodies revealed anti-rhesus D specificity, which had to be interpreted either as an autoantibody of patient's origin or, hypothetically, as a "graft versus host" antibody of donor origin. Gm- and Km allotyping of these antibodies demonstrated a pattern which differed from the patient's but was identical to that of the kidney donor. Therefore hemolysis could be explained unambiguously by "graft versus host" antibodies. Whether the thrombocytopenia was also due to an immune process was not clear, although some evidence favors this hypothesis. Immunosuppressive treatment remained unchanged and several red blood cell transfusions were necessary before reactivity of the direct antiglobulin test diminished and became negative 7 weeks after kidney transplantation. The occurrence of hemolysis in the early posttransplantation period should thus draw attention to the possibility of "graft versus host" antibodies directed against red cells. Concomitant thrombocytopenia may occur. Donor screening for irregular erythrocyte antibodies should be performed whenever solid organ transplantation is intended.

HLA antibody screening is conducted routinely prior to kidney transplantation, but the comparative prognostic value and cost-effectiveness of different methods are unclear. Pre-transplant sera of 141 patients transplanted between 1998 and 2000 were screened by ELISA and Luminex assays, and antibody specificities of reactive sera determined using bead array techniques. ELISA screening detected donor-specific antibodies (DSA) in 19 patients, who had a higher incidence of impaired graft function (60% vs. 20%, p = 0.04) and antibody-mediated rejection (AMR) within 90 d after transplantation (AMR, 35% vs. 5%, p = 0.02). Luminex screening detected eight additional patients with DSA, among those one with AMR. Six of eight patients with Luminex-only-DSA reported no prior immunizing events. Death-censored graft survival was shorter only in patients with DSA and AMR (median, 1.7 yr instead of between 9.5 and 11.0 yr for patients without DSA or patients with DSA but no AMR, p < 0.001). Material costs per detected clinically relevant DSA were about 57% higher for Luminex screening, but this increase could be avoided by modifying the cut-off recommended by the manufacturer. Conclusively, specification of antibodies only in sera reactive in screening tests was cost-effective to prevent shortened graft survival. Preformed DSA were only harmful if AMR was diagnosed within 90 d after transplantation.

BACKGROUND: Chronic allograft nephropathy (CAN) is a multifactorial process with immunologic and nonimmunologic factors. Because tacrolimus (Tac) has been ascribed a beneficial effect on some of these factors when compared to cyclosporine A (CyA), a randomized controlled trial was conducted to investigate whether conversion from CyA to Tac can ameliorate the progression of renal dysfunction in kidney transplant recipients (KTR) with CAN. METHODS: Of the 46 patients with biopsy-proven CAN enrolled, 24 were converted from CyA to Tac, whereas 22 patients were maintained on CyA. Serum creatinine (SCrea), lipid profiles and an antihypertensive score (AHS) were determined after 3, 6 and 12 months. AHS is based on the total number and dosages of antihypertensive medications used. SCrea and AHS were additionally evaluated at 36 months. RESULTS: SCrea was decreased in the Tac group (Tac(baseline): 297 +/- 67 micromol/L; Tac(6): 261+/- 70 micromol/L, P < 0.001; Tac(12): 254 +/- 55 micromol/L, P < 0.001; Tac(36): 255 +/- 78 micromol/L, P = 0.235), whereas a significant increase of SCrea was detected in the CyA group (CyA(baseline): 279 +/- 77 micromol/L, CyA(12): 333 +/- 98 micromol/L, P < 0.001; CyA(36): 317 +/- 89 micromol/L, P < 0.001). Compared to CyA therapy, SCrea in the Tac group declined after 12 and 36 months (P = 0.011 and 0.048, respectively) as well as AHS (Tac(12): 59 +/- 13, CyA(12): 83 +/- 14, P < 0.001; Tac(36): 60 +/- 12, CyA(36): 84 +/- 14, P < 0.001). LDL cholesterol was lower in the Tac group after 12 months (Tac(12): 2.5 +/- 0.5 mmol/L, CyA(12): 3.5 +/- 0.6 mmol/L, P < 0.001). CONCLUSION: Conversion from CyA to Tac in KTR with CAN improves allograft function, lowers blood pressure, and reduces LDL cholesterol. This superior profile may translate into improved long-term graft survival.

Recently, we demonstrated an association of the IL-6 promoter polymorphism at position -174 (G-->C) with kidney allograft survival whereby carriers of the -174GG genotype were identified as having superior graft survival. As two additional polymorphisms were discovered in the neighborhood at positions -572 (G-->C) and -597 (G-->A), respectively, and as functional studies revealed a cooperative impact of all three on the IL-6 gene transcription, we investigated whether there is a combined effect on kidney transplant outcome. We determined IL-6 promoter haplotypes -597 (G-->C)/-572 (G-->A)/-174 (G-->C)(-597/-572/-174haplotype) using a PCR system with sequence-specific primers in 158 patients after primary cadaveric kidney transplantation. We here show that the -597 and -174 polymorphism are in tight-linkage disequilibrium and that homozygous carriers of the GGG-597/-572/-174 haplotype (GGG/GGG genotype) have superior 3-year graft survival rates compared with the 8.0-fold increased risk of premature graft loss in all other patients. Interestingly, patients carrying the GGG/GCG genotype had the lowest allograft survival rate. Thus determination of the combined -597/-572/-174 genotype allows for further differentiation of -174GG patients into subgroups and consequently for a more accurate identification of patients at risk. Our results indicate that the three polymorphisms act in a cooperative fashion and we provide evidence for an exceptional clinical impact of the IL-6-597/-572/-174 genotype on the success of kidney transplantation.

Analgesic abuse is a potential cause of end-stage renal disease. Such patients bear an elevated risk of developing malignancies, predominantly transitional-cell carcinoma. We report our experience with laparoscopic nephroureterectomy carried out in patients with analgesic nephropathy to exclude upper urinary tract malignancy. All patients were scheduled to be put on the waiting list for cadaveric renal transplantation.Since 1996, nine women and two men with a long-term history of analgesic abuse have undergone laparoscopic nephroureterectomy at our hospital. The median age was 63 years (range 51-70 years). All patients had developed end-stage renal failure secondary to heavy analgesic abuse with a median duration of 14 years (range 7-40 years). The median interval from the beginning of hemodialysis to laparoscopic nephroureterectomy was 36 months (range 6-76 months).The median operative time was 99 minutes (range 55-170 minutes). There were no conversions to open surgery. Two complications occurred, and three patients required blood transfusions. The median hospital stay lasted 5 days (range 2-12 days), and the median convalescence was 20 days (range 6-44 days). In seven patients, histopathologic examination of the kidney revealed changes attributable to analgesic abuse. None of the patients had a transitional-cell carcinoma, but in two patients, a renal-cell carcinoma stage pT1cN0cM0 grade 2 was detected.Patients with analgesic nephropathy bear an elevated risk for the development of transitional-cell or renal-cell carcinoma. In these patients, laparoscopic nephroureterectomy combines minimally operative invasiveness with a maximum of diagnostic safety.

A lymphocele is a common finding after renal transplantation and occurs in up to 20% of patients. The majority of patients are asymptomatic. However, once a lymphocele has become symptomatic (e.g., through transplant dysfunction) this condition has to be treated. We report our 9-year experience with laparoscopic lymphocele fenestration and discuss the current management options for posttransplant lymphoceles.Since 1993, 19 patients (11 males and 8 females; median age 56 years, range 22-68 years) of a total of 31 patients with a symptomatic posttransplant lymphocele have undergone laparoscopic fenestration of their lymphocele at a median of 66 days (range, 19-111 days) following successful renal transplantation in our department. As a first-line treatment, a percutaneous pigtail drainage catheter was inserted in all patients. In case of failure in resolving the fluid collection, the next step included sclerotherapy by instillation of tetracycline or ethanol into the lymphocele cavity in some cases. In patients with a persistent lymphocele, a laparoscopic lymphocele fenestration via a transabdominal approach was undertaken to achieve adequate drainage.Primary laparoscopic lymphocele fenestration was successful in all except two patients, who required a conversion. The median operating time was 36 min (range, 20-70 min). Following the procedure, renal transplant function remained stable or returned to individually normal levels in all patients. Median duration of hospital stay was 4 days (range, 1-13 days). At median follow-up of 27 months, all patients were alive with a functioning transplant.Laparoscopic lymphocele fenestration is reserved for patients in whom temporary drainage with or without sclerotherapy failed to resolve the fluid collection. In these cases the laparoscopic approach offers obvious technical and clinical advantages compared to open operative techniques.

Primary hyperoxaluria type 1 (PH1) is caused by deficiency of peroxisomal alanine-glyoxylate aminotransferase which is in humans exclusively expressed in liver cells. The disease is inherited as an autosomal recessive trait, and initial symptoms usually occur in early childhood. Up to the age of 25 years, 90% of the patients are symptomatic, and many patients develop end-stage renal failure. Pronounced medical care is necessary in PH1 patients to prevent generalized oxalosis with complications due to bone disease and peripheral gangrene. The rather short survival of patients on hemodialysis is caused by sudden arrhythmias and heart block. As no dialysis procedure is able to remove the daily produced oxalate, early transplantation is mandatory. Our 45-year-old patient is remarkable on the basis of the late manifestations of PH1. The diagnosis was delayed by unspecific symptoms of nephrolithiasis with recurrent pyelonephritis. Clinical course and diagnostic cornerstones of primary hyperoxaluria are outlined. The principles of conservative treatment and experiences with dialysis and transplantation are discussed.

Background Laparoscopy is believed to result in possible clinical benefits for the patient. We report our experience with renal laparoscopy in dialysis patients and compare the results with those from non-dialysis patients. Methods Between December 1994 and April 1997, 19 dialysis patients underwent laparoscopic nephrectomy or nephroureterectomy at our hospital. The group consisted of 11 female and eight male patients (mean age 45 years). In nine patients the indication for nephrectomy was chronic pyelonephritis. Nephroureterectomy for vesicoureteral reflux with recurrent episodes of pyelonephritis or analgesic nephropathy for exclusion of transitional cell carcinoma of the upper urinary tract was considered in nine other patients. Laparoscopic bilateral nephrectomy for drug-resistant hypertension was performed in one patient. In comparison, a consecutive group of non-dialysis patients who had undergone renal laparoscopy was reviewed. Results In the dialysis group, one patient had to be converted to open nephrectomy due to bleeding. Six dialysis patients required blood transfusions compared with none in the non-dialysis group. There were four complications in the dialysis group and two in the non-dialysis group. Both groups had comparable results for operative times, analgesic consumption, postoperative start of oral intake and mobilization, and duration of hospitalization and convalescence. Conclusions Laparoscopic nephrectomy in dialysis patients has acceptable results. The higher transfusion rate is probably due to a lower preoperative haemoglobin and is not aggravated by possible affects of the clotting system in patients with chronic uraemia.

BACKGROUND Hypertension is an important risk factor for the development of chronic graft failure and decreased graft and patient survival after renal transplantation. METHODS Between September 1994 and August 1996, 14 patients underwent laparoscopic bilateral nephrectomy for treatment of drug-resistant hypertension after successful renal transplantation. Common causes of hypertension were largely excluded before bilateral nephrectomy. A scoring system was developed for comparison of different antihypertensive regimes. In this system, points were given according to type and dosage of each antihypertensive drug. RESULTS At 6-month follow-up, all patients showed well-controlled blood pressure (median of mean arterial pressure: 104 vs. 130 mmHg preoperatively, P

We report our experience with laparoscopic nephroureterectomy for benign disease and compare the results to a contemporary group of patients undergoing open nephroureterectomy.Between October 1994 and March 1997, 12 women and 4 men with a mean age of 50 years (range 22 to 70) underwent laparoscopic nephroureterectomy at our hospital. Indications for operation were nonfunctioning kidneys due to vesicoureteral reflux with recurrent episodes of pyelonephritis or analgesic nephropathy before a planned renal transplantation. In comparison 11 women and 4 men with a mean age of 40 years (range 18 to 64) underwent open nephroureterectomy for various benign diseases.Laparoscopic and open nephroureterectomy had no significant differences regarding operative times (100 versus 124 minutes) and complication rates (25 versus 20%). In the laparoscopy group conversion to open surgery was not necessary. Patients who underwent laparoscopic nephroureterectomy had significantly less consumption of morphine equivalent for postoperative pain control (12 versus 40 mg.), shorter time to achieve mobilization and oral intake (11 versus 39 hours), shorter hospital stay (6 versus 12.7 days) and faster return to normal activities (21 versus 39 days).Laparoscopic nephroureterectomy in patients with benign disease has similar operative results but obvious postoperative advantages compared to the open approach.

Previous investigations have shown that the determination of two acute-phase proteins in the urine, C-reactive protein (CRPu) and alpha2-macroglobulin (alpha2-MGu), allows a noninvasive diagnosis of acute renal graft dysfunction. A reliable differentiation between rejection and urinary tract infection can be made only when considering the C-reactive protein in serum and urine at the same time (CRPs:CRPu ratio). Therefore, a diagnostic procedure independent of parameters other than urinary proteins is needed. As granulocytes play only a minor role in graft rejection but are a common feature in urinary tract infection, we determined a marker of granulocytes (myeloperoxidase) in urine (MPOu). Eighty-nine renal transplant recipients were included in the study. In normal courses, CRPu, alpha2-MGu, and MPOu were within the normal range. In 15 cases of acute interstitial rejection, an increased excretion of CRPu and alpha2-MGu could be confirmed, but MPOu could not be detected. On the occasion of acute vascular rejection (n=6), with the exception of one case, MPOu could not be observed. The pattern of the three urinary proteins differed in urinary tract infections (n=40): MPOu could be detected in all cases, CRPu in 50% of cases, and alpha2-MGu in 73% of cases. In patients with cytomegalovirus infection (n=7), no MPOu, CRPu, or alpha2-MGu was found. In conclusion, the simultaneous measurement of the three proteins allows a complete, noninvasive, differential diagnostic procedure of renal graft dysfunction.

Primary immunosuppressive therapy in renal transplantation is mediated by glucocorticosteroids with a delay of several hours. Consequence of the common practice of using first dose of steroids intraoperatively is a first contact of antigens with an unaltered immune system. In a prospective study on 111 renal transplant patients, we could show by the parameters of in vitro cytocine generation and acute rejection episodes that immunological responsivenes can be altered by early (5 h) preoperative use of glucocorticosteroids.

Reactivation of the Epstein-Barr virus was reported to occur frequently under immunosuppressive therapy following organ transplantation. However, little is known about the clinical significance of these EBV reactivations. Therefore, we searched for correlations among the treatment with various immunosuppressive drugs, the incidence of CMV infections, rejection crises, and serological signs of EBV reactivation. EBV-specific antibodies were measured with novel ELISAs, utilizing the recombinant antigens p72 (for anti-EBV nuclear antigen [EBNA]1-IgG), p54, and p138 (anti-early antigen [EA]-IgM, -IgG, -IgA) in a follow-up study of 79 renal transplant recipients. Patients receiving antithymocyte globulin or antilymphocyte globulin therapy showed increasing anti-EA-IgG and -IgA more often than did patients not receiving antithymocyte globulin or antilymphocyte globulin therapy (P < 0.05). In patients receiving OKT3 antirejection therapy, anti-EA-IgM seroconversion was found more frequently (P < 0.01). A significant correlation was also found between groups of patients who had had at least one rejection episode versus patients without any sign of organ rejection, and the incidence of increasing anti-EA-IgG (P < 0.05). Since in most of these patients signs of EBV reactivation followed the appearance of the rejection episode, this may not be due to viral-induced rejection but may be caused by the reinforced immunosuppression during antirejection therapy. As opposed to patients with no signs of CMV infection and with nonsymptomatic CMV infection, patients undergoing symptomatic CMV infection showed anti-EA-IgM seroconversion (P < 0.01), increasing anti-EA-IgA (P < 0.01), and decreasing anti-EBNA-IgG (P < 0.01) more frequently. Our results confirm the role of immunosuppressive therapy in the pathogenesis of EBV reactivation. We further demonstrate a striking coincidence of EBV reactivation and symptomatic CMV infection.

A total of 30-50% of all renal transplant recipients undergo infections caused by human cytomegalovirus. With the introduction of ganciclovir and foscarnet for specific antiviral therapy there is an increasing demand for diagnostic tools that allow the early and rapid identification of CMV as the causative agent of the observed disease. We and others previously showed the direct detection of pp65 antigen in peripheral blood leukocytes to be an excellent marker for active cytomegalovirus infection. In order to establish whether the detection of CMV DNA by the polymerase chain reaction (PCR) supplies further information in this regard, we compared both methods. In 41 renal transplant patients the PCR assay yielded a sensitivity of 100% compared with 87.5% of the antigenemia assay. Specificities reached 67% and 92.5%, respectively. In 5 patients without both serological signs of infection and antigenemia, CMV DNA was also found. The duration of CMV DNA detection in PBL during active infection was significantly longer than antigenemia. Even after successful treatment of symptomatic CMV disease, DNA was present for a period of weeks without any relapse of disease. In contrast, antigenemia disappeared after antiviral therapy and reappeared only in one patient with relapse of CMV disease. We conclude that PCR offers no advantages over antigen detection in monitoring for CMV infections after renal transplantation.

The frequency of cytomegalovirus infection was studied in a prospective study of 106 kidney recipients. The detection of cytomegalovirus-immediate-early-antigen and cytomegalovirus-immunoglobulin (IgM) antibodies in serum was used as the reference method and showed that 23.6% (25/106) of all patients were infected. In addition, four urinary proteins (IgG and transferrin as glomerular markers and α1-microglobulin and β2-microglobulin as tubular markers) were quantitatively measured in 24-h urine samples from all of the patients using an immunoluminometric assay (ILMA). In all cytomegalovirus infection cases a pronounced but isolated increase of urinary β2-microglobulin excretion was observed. In 20 of 25 infected patients, the p2-microglo-bulinuria occurred 1–21 days (median 5.0) earlier than the appearance of the cytomegalovirus-immediate-early-antigen in blood. Thus, it can be seen that the quantitative measurement of β2-microglobulin in urine is useful for the early detection of cytomegalovirus infection following renal transplantation.