Reinhard Brunkhorst

Discrimination of infectious and noninfectious causes of early acute respiratory distress syndrome by procalcitonin

OBJECTIVE To test the sepsis marker procalcitonin (PCT) for its applicability to discriminate between septic and nonseptic causes of acute respiratory distress syndrome (ARDS). DESIGN Prospective study, assessing the course of PCT serum levels in early (within 72 hrs after onset) ARDS. The three other inflammation markers neopterin, interleukin-6 (IL-6), and C-reactive protein (CRP) were tested in parallel. SETTING Twenty-four-bed medical intensive care unit of a 1,990-bed primary hospital, providing health care for an estimated 39,000 patients. PATIENTS Twenty-seven patients, 18 male and nine female, aged 16-85 yrs, with early ARDS of known cause (17 with septic and ten with nonseptic ARDS) were enrolled in a prospective study between May 1994 and May 1995. INTERVENTIONS Serum samples were drawn every 4-6 hrs for measurement of PCT, neopterin, IL-6, and CRP concentrations. Blood cultures, tracheal aspirates, and urine samples were obtained every 12-24 hrs. In 24 of 27 patients, bronchoscopic cultures were also obtained. Clinical sepsis criteria as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference were checked daily. MEASUREMENTS AND MAIN RESULTS Assessment of inflammation marker serum levels in septic vs. nonseptic ARDS. PCT serum levels were significantly higher (p < .0005) in the patients with septic ARDS than in patients with nonseptic ARDS within 72 hrs after onset of ARDS. There was no overlap between the two groups. Also, neopterin allowed a differentiation (p < .005), although a substantial overlap between serum levels of septic and nonseptic patients was observed. No discrimination could be achieved by determination of CRP and IL-6 levels. CONCLUSION PCT determination in early ARDS could help to discriminate between septic and nonseptic underlying disease.

Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolytic–uraemic syndrome: an analysis of the German STEC-HUS registry

BACKGROUND May 22nd marks the beginning of a Shiga-toxin-producing Escherichia coli (STEC) O104:H4 outbreak in Northern Germany. By its end on 27 July, it had claimed 53 deaths among 2987 STEC and 855 confirmed haemolytic-uraemic syndrome (HUS) cases. METHODS To describe short-term effectiveness of best supportive care (BSC), therapeutic plasma exchange (TPE) and TPE with eculizumab (TPE-Ecu) in 631 patients with suspected HUS treated in 84 hospitals in Germany, Sweden and the Netherlands using the web-based registry of the DGfN (online since 27 May). RESULTS Of 631 entries, 491 fulfilled the definition of HUS (median age 46 years; 71% females). The median (inter-quartile range) hospital stay was 22 (14-31) days. Two hundred and eighty-one (57%) patients underwent dialysis and 114 (23%) mechanical ventilation. Fifty-seven patients received BSC, 241 TPE and 193 TPE-Ecu. Treatment strategy was dependent on disease severity (laboratory signs of haemolysis, thrombocytopenia, peak creatinine level, need for dialysis, neurological symptoms, frequency of seizures) which was lower in BSC than in TPE and TPE-Ecu patients. At study endpoint (hospital discharge or death), the median creatinine was lower in BSC [1.1 mg/dL (0.9-1.3)] than in TPE [1.2 mg/dL (1.0-1.5), P < 0.05] and TPE-Ecu [1.4 mg/dL (1.0-2.2), P < 0.001], while need for dialysis was not different between BSC (0.0%, n = 0), TPE (3.7%; n = 9) and TPE-Ecu (4.7%, n = 9). Seizures were absent in BSC and rare in TPE (0.4%; n = 1) and TPE-Ecu (2.6%; n = 5) patients. Total hospital mortality in HUS patients was 4.1% (n = 20) and did not differ significantly between the TPE and TPE-Ecu groups. CONCLUSIONS Despite frequent renal impairment, advanced neurological disorders and severe respiratory failure, short-term outcome was better than expected when compared with previous reports. Within the limitations of a retrospective registry analysis, our data do not support the notion of a short-term benefit of Ecu in comparison to TPE alone in the treatment of STEC-HUS. A randomized trial comparing BSC, TPE and Ecu seems to be prudent and necessary prior to establishing new treatment guidelines for STEC-HUS.

Recurrent immunoglobulin A nephropathy after renal transplantation: a significant contributor to graft loss.

BACKGROUND Although most transplanted patients with underlying IgA nephropathy (IgAN) develop histological recurrence, its clinical relevance is considered low. METHODS We performed a single-center analysis of 61 renal transplant patients with IgAN. RESULTS Forty-four percent of the patients showed a stable graft function. Progressive graft dysfunction apparently due to recurrent IgAN occurred in 23% of the patients (16% required dialysis). Five patients were retransplanted, and three again developed dialysis-dependent renal failure apparently due to recurrent IgAN. In 20% of the patients, chronic transplant dysfunction was due to other reasons, whereas no reason was identified in 13% of the patients. Neither findings before transplantation, the ACE genotype, the type of immunosuppression, nor the course after transplantation predicted transplant dysfunction due to recurrent IgAN. Follow-up after transplantation was longer in the group with dysfunction due to recurrent disease than in the group with dysfunction due to chronic rejection or in the stable group. CONCLUSION Recurrent IgAN is a clinically relevant problem in renal transplant patients. Its importance may have been underestimated in the past due to inadequate lengths of follow-up.

Incidence of Pneumocystis carinii pneumonia after renal transplantation : Impact of immunosuppression

The incidence and potential risk factors of Pneumocystis carinii pneumonia (PCP) in our population of renal transplant recipients were analyzed retrospectively. Of 1427 patients who received transplants between January 1986 and June 1994, 1192 were evaluated. Four different immunosuppressive regimens were applied: (1) cyclosporine (CsA) + prednisolone (Pred), (2) CsA + azathioprine (Aza, 2 mg/kg/day) + Pred, (3) CsA + Aza + antithymocyte globulin, and (4) (after December 1, 1993, European multicenter trial) FK506 + Aza (1 mg/kg/day) + Pred. No prophylaxis against PCP was performed. Before December 1, 1993, three PCPs in 494 patients on protocol 2 or 3 occurred (0.6%). Afterward, seven PCPs in 77 patients occurred (9%): three in 38 patients on protocol 2 (7.8%) and four in 28 patients on protocol 4 (14.3%). Comparing patients with PCP on CsA and FK506, the mean Aza dose was 2.40 and 1.32 mg/kg/day, five and two patients received additional steroids, antibody treatment was used in three and no patients, and CMV infections occurred in five and two patients, respectively. The incidence of PCP with a moderate CsA-based immunosuppressive regimen is low and seems to occur only in cases of additional immunosuppressive cofactors. Despite a general increase of PCP, its incidence was highest in patients on FK506 with fewer immunosuppressive cofactors. Thus, prophylaxis against PCP after renal transplantation should be performed, if not in every renal transplant recipient, at least in case of treatment with additional steroids, antibodies, or FK506.

Renal transplantation in older adults: is graft survival affected by age? A case control study.

BACKGROUND The demand for kidney allografts in older patients is growing continually. Previously published data indicate that the higher rate of graft losses resulting from the age-related increased mortality in older transplant recipients is balanced by a significantly lower number of graft losses from immunological problems (acute and chronic rejection) in old patients. This single center study was performed to scrutinize these results with the methods of a case control analysis. METHODS Ninety-one patients, 65 years and older (mean age 67), were included in the case group. Their data were compared with those obtained from two control groups, 40-55 and 18-35 years old, respectively (mean ages 48 and 29, respectively). Apart from age, the groups were matched with regard to HLA-mismatches and date of transplantation. RESULTS The number of initially non-functioning grafts and donor age did not differ significantly between the case and the control groups. During the follow-up of 5 years, acute rejections were significantly more frequent in the older control group. In contrast to previous studies, however, graft losses caused by rejections were not significantly more frequent in younger patients than in transplant recipients over age 65 years. Thus, as a consequence of increased patient mortality, the total graft survival in the case group was significantly worse than in the control groups. CONCLUSIONS In the presence of organ shortage, an indication for kidney transplantation in patients over 65 years has to be considered carefully because age did not prove to have a beneficial effect on graft survival. Nevertheless, patients of this age group should not be excluded from renal transplantation, because not only medical, but also ethical, issues are involved.

Renal transplantation for patients with autoimmune diseases: single-center experience with 42 patients.

BACKGROUND In patients with autoimmune diseases such as vasculitis or systemic lupus erythematosus (SLE), end-stage renal disease develops in a high percentage of patients, and kidney transplantation has become a therapeutic option. However, only limited data about the prognosis and outcome after kidney transplantation are available. METHODS Long-term graft survival and graft function of renal transplant recipients with SLE, Wegeners granulomatosis, microscopic polyangiitis, Goodpastures syndrome, and Henoch-Schonlein purpura were evaluated in a single center. In addition, the incidence of renal and extrarenal relapses and the impact of the immunosuppressive therapy on the course of the autoimmune disease were studied. RESULTS Renal transplant recipients with autoimmune diseases such as vasculitis and SLE had a patient survival rate (94% after 5 years) and a graft survival rate (65% after 5 years) comparable to those of patients with other causes of end-stage renal disease (patient survival 88% and graft survival 71% after 5 years). Graft losses due to the underlying disease were rare. Extrarenal relapses occurred in three patients with Wegeners granulomatosis, one patient with microscopic polyangiitis, and three patients with SLE, but were less frequent compared with the period with chronic dialysis therapy. Autoantibody levels in patients with SLE, Wegeners granulomatosis, or microscopic polyangiitis did not seem to influence the outcome. CONCLUSIONS Renal transplantation should be offered to patients with autoimmune diseases. Follow-up should include the short-term control of renal and extrarenal disease activity.

Improved survival in patients with type 1 diabetes mellitus after renal transplantation compared with hemodialysis: a case-control study.

Background. Diabetes mellitus is the leading cause of renal failure worldwide. The question of which treatment modality—hemodialysis versus renal transplantation—is associated with the lowest risk of cardiovascular morbidity and mortality in the diabetic end‐stage renal disease (ESRD) population has not yet been investigated in a controlled trial. Methods. We therefore conducted a case‐control study of patients with ESRD caused by type 1 diabetes mellitus. The case patients were diabetics who received a renal graft between 1978 and 1997, whereas the controls were registered for renal transplantation but stayed on maintenance hemodialysis without ever undergoing transplantation. The groups were matched for age, sex, duration of diabetes, length of hemodialysis (up to the registration), and date of registration for renal transplantation. Results. Kaplan‐Meier life table analysis, based on 46 case patients and 46 controls, demonstrated a highly significant (P=0.0001) poorer survival in the control group compared with the case group. Logistic regression showed that hemodialysis was a significant risk factor for death (P=0.0002) and cardiovascular morbidity (P=0.0023). Patients with cardiovascular complications such as coronary artery and peripheral vascular events were significantly more frequent in the control group. Additionally tested risk factors for cardiovascular complications (serum cholesterol, arterial blood pressure, number of antihypertensive drugs, serum calcium, serum phosphate, and glucose control [hemoglobin A1c]) showed no significant correlation to survival or morbidity in either group by logistic regression. Conclusions. Renal transplantation is associated with a significantly improved survival compared with hemodialysis in patients with ESRD caused by type 1 diabetes mellitus. This seems to be a result of a reduced incidence of cardiovascular complications after renal transplantation.

How best to use tacrolimus (FK506) for treatment of steroid- and OKT3-resistant rejection after renal transplantation.

Nineteen patients with biopsy-confirmed ongoing acute rejection of renal allografts were converted from standard immunosuppression to FK506. Eight grafts showed vascular rejection and 11 had cellular rejection on biopsy. All patients had already received intravenous high-dose steroid treatment. Ten patients also had additional OKT3 rescue therapy. Initial FK506 doses were 0.13 +/- 0.06 mg/kg/day; the FK506 whole blood trough level after 3 days of treatment was 9.3 +/- 4.5 ng/ml. After conversion to FK506 all but four patients also received azathioprine, 1.5-2 mg/kg/day, and all patients received oral prednisolone. Concomitant with initiation of FK506, an anti-infective prophylaxis was prescribed, consisting of ganciclovir and trimethoprim/sulfamethoxazole. Sixteen out of 19 of the grafts (84%) were rescued successfully, including two grafts of patients already on hemodialysis at the time of conversion. Graft function of the responders improved from an average serum creatinine level of 364 +/- 109 mumol/L to 154 +/- 49 mumol/L. Of the patients receiving high-dose steroids alone prior to FK506 initiation, 8/9 responded to FK506 treatment, compared with 8/10 of those who had also received OKT3. During the mean follow-up of 35 weeks after conversion, no clinically apparent cytomegalovirus infection and no pneumonia were seen. Treatment with FK506 may successfully suppress ongoing acute rejection, even if antilymphocyte preparations have failed. FK506 can be used at a lower dose than so far recommended without impairing the antirejection potential. An additional anti-infective prophylaxis seems effective in preventing severe complications in the first months after rejection therapy.

Five Cases Of Kaposi's Sarcoma In Kidney Graft Recipients: Possible Influence of the Immunosuppressive Therapy

BACKGROUND Kaposis sarcoma (KS) is an human herpesvirus 8-associated tumor, occurring in immunocompromised patients. We report here an increased incidence of KS among kidney graft recipients (KGRs) during the last 2 years, concomitant to the introduction of the immunosuppressant mycophenolate mofetil (MMF). METHODS A total of 1835 KGRs, receiving organs between 1987 and 1997, were surveyed for the development of KS. A total of 371 patients received therapy including MMF (group A), whereas 1464 patients were treated with an MMF-free protocol (group B). RESULTS 3/371 patients (0.8%) of group A versus 2/1464 patients (0.1%) of group B developed KS. In group A, KS became evident 7+/-2 months after initiation of MMF therapy. CONCLUSIONS At our center, during the last 2 years, the incidence of KS has increased in KGRs, and it is not clear whether the introduction of MMF contributes to the phenomenon.

Attitudes of patients before and after transplantation towards various allografts.

BACKGROUND The presence of an allogeneic graft inside the body may have psychological impact on transplant patients. It was the aim of this study to evaluate the attitude of patients before and after different types of organ transplantation towards organ allografts. METHODS A total of 1,049 patients (722 patients after and 327 patients on the waiting list for either kidney, liver, heart, or lung transplantation) under care of a single transplant center were studied using a questionnaire with blinded analysis of the data. Mental condition of the patients, their attitude towards the allograft and its donor, emotional stress caused by a graft, and correlation of the attitudes with clinical and demographic parameters were analyzed. RESULTS The self-reported mental condition of the patients was markedly and consistently better after organ transplantation; 27% of patients before and 60% after transplantation were in good mental condition. Sixty-two percent of transplant patients considered the graft as their own organ, 37% regarded it as a foreign organ now belonging to their body, and 1% considered it as a foreign body; among waiting list patients, 40%, 55%, and 5% assumed they would perceive their graft accordingly. The graft caused considerable emotional stress for 2% of transplant patients, whereas for 70% it did not cause any stress; the latter was assumed by 47% of patients before transplantation. Eleven percent of transplant patients frequently think about the origin of their graft, and 30% would like to have information about their donor. Knowledge about different religion, opposite sex, homosexuality, suicidal death, and age above 65 years of their donor would be of moderate or major concern for 0%, 3%, 21%, 24%, and 38% of the patients, respectively. CONCLUSIONS The comprehensive survey shows that transplant patients incorporate their graft well into their body image. Emotional stress caused by the graft is very low and is generally less than assumed before transplantation. Knowledge about certain characteristics of the donor may cause increased concerns in some patients.