Fatal cytomegalovirus pneumonia after preemptive antiviral therapy in a renal transplant recipient.

Cytomegalovirus (CMV) infections occur with an incidence of up to 70% in renal transplant patients and mortality is low due to effective antiviral drugs. We report here the case of a patient who suffered from an uncommonly severe and therapy-resistant pulmonary CMV infection. During the disease course, CMV-PCR from alveolar cells and lung biopsy material was repeatedly negative despite high CMV pp65 antigenemia. CMV pneumonia was finally diagnosed from a biopsy obtained by open thoracotomy revealing positive CMV immunostaining of lung tissue. The patient died of respiratory failure though double-treatment using both ganciclovir and foscavir was administered. Post mortem, the clinically suspected resistance to both antiviral drugs, but not to cidofovir, could be proven by bioassay testing of in vitro growth responses using viral cultures. CMV pneumonia may thus not be diagnosed by standard PCR techniques in rare cases and may be resistant to the available antiviral therapy. Severe CMV pneumonia may benefit from novel antiviral drugs such as cidofovir, which is currently used in the treatment of CMV retinitis in HIV patients.

Heparin-free hemodialysis with prophylactic change of dialyser and blood lines.

Heparinization during hemodialysis may cause severe bleeding complications in patients with high bleeding risk. Heparin-free hemodialyses (n = 208) were performed in 46 unselected patients with high bleeding risk after kidney transplantation (n = 25), after major surgery (n = 10), and with bleeding disorders (n = 11). Dialyser and blood lines were primed without heparin. In addition to the established measures (high blood flow, intermittent rinsing), system clotting was prevented by prophylactically changing the dialyser and blood lines in 107 of 208 dialyses (52 percent). Total system clotting with blood loss ranging from 100 to 250 ml occurred in six cases (3 percent). Mean hemodialysis time (+/- SD) was 4.1 hours (+/- 0.4), rising volume of the extracorporeal system 1.4 liters/hour (+/- 0.6), blood flow 244 ml/min (+/- 38), clotting time 12 min (+/- 4), and weight loss 2.5 kg (+/- 1.5). Mean hemodialysis creatinine clearance was 110 ml/min (+/- 34) and BUN clearance 138 ml/min (+/- 48). Heparin-free hemodialysis with prophylactic change of system is thus a safe and practical method of treatment for patients at high bleeding risk, but it is less effective, more expensive and the patient requires closer care.

Incidence of analgesic nephropathy in Berlin since 1983.

BACKGROUND: Phenacetin was removed from the German market in 1986 and was replaced mainly in analgesic compounds by acetaminophen. Our objective was to examine the effect of this measure on the incidence of analgesic nephropathy in light of the changes in other end-stage renal diseases. METHODS: We therefore compared the proportion of renal diseases in all patients starting dialysis treatment during three 18-month periods: 4/1982-9/1983 (n=57); 1/1991-6/1992 (n=81); and 10/1995-3/1997 (n=76). RESULTS: On the one hand, the proportion of end-stage analgesic nephropathy decreased significantly from 30% in 1981-1982 to 21% in 1991-1992 and 12% in 1995-1997 (P=0.01). On the other hand, type II diabetes increased significantly from 7% to 22% (P=0.01) and 29%, (P=0.001). Using the chi2 distribution test to analyze the frequencies of seven diseases at three different time intervals, however, showed that the changes in renal-disease proportions between 1982-1983, 1991-1992 and 1995-1997 were not significantly independent. There was a significant median age increase from 52 years (CI0.95 44-58) in 1982-1983 to 63 (CI0.95 55-67) in 1991-1992 and 63 (CI0.95 60-66) in 1995-1997 (P=0.003) for all patients starting dialysis but not for those with analgesic nephropathy [59 (55-71) vs 64 (53-67) and 61 (50-72); n.s.]. CONCLUSION: The decrease of end-stage analgesic nephropathy since 1983 may be partially due to the removal of phenacetin from the German market in 1986. However, considering the general increase in numbers of dialysis patients, their higher age and the increased incidence of type II diabetes, the decrease in analgesic nephropathy is not a statistically significant independent variable. Altered admittance policies for dialysis treatment have yielded a new pattern of renal-disease proportion which interferes with changes in the incidence of analgesic nephropathy.

Risk factors of system clotting in heparin-free haemodialysis.

Heparin-free haemodialysis must be considered for all dialysis patients with a risk of haemorrhage. This technique is associated with increased danger of system coagulation with a blood loss of up to 250 ml. In 84 patients with a risk of haemorrhage, 296 heparin-free haemodialyses were recorded prospectively. First signs of coagulation were found very much more frequently in the venous airtrap than in the dialyser (146 vs 42). System coagulation occurred in 13 of the 296 dialyses (4%) and was prevented by prophylactic switching of the system and dialyser in 140 dialyses (47%). The time of system coagulation was on average 1.8 hours (+/- 0.2) after the beginning of dialysis. The 13 patients with system coagulation had a reduced blood flow on dialysis (217 +/- 52 vs 240 +/- 36 ml/min). Their initially normal clotting time (12 +/- 5 vs 14 +/- 4 min) was more significantly shortened after 2 h (4 +/- 3 vs 8 +/- 3 min). The activities of antithrombin III (87 +/- 34% vs 88 +/- 39%) and protein C (66 +/- 45% vs 59 +/- 37%) do not differ from those of 47 other patients, even at the time of system coagulation, as measured in five patients (92 +/- 34% for antithrombin III, 51 +/- 29% for protein C). System coagulation and shortening of clotting time thus cannot be regarded as a consequence of absorption of these inhibitory factors of plasmatic coagulation. The danger of system coagulation in heparin-free haemodialysis could probably be further reduced by an improvement of the biocompatibility of systems (airtrap) and dialysers (less activation of thrombocytes).

Plasma exchange and hemoperfusion in iodine-induced thyrotoxicosis.

Iodine-induced thyrotoxicosis is a life-threatening disease. Plasma exchange and hemoperfusion are the available means of detoxication. Both methods were applied repeatedly to 4 patients with iodine-induced thyrotoxicosis, and the efficacy of these treatment methods was compared. Thyroxine plasma levels were decreased by 33%, while the calculated body stores were reduced by 18% during plasma exchange. Hemoperfusion was less effective. With both methods, a rebound of plasma levels was seen. Improvement of the clinical condition was delayed for 1 week after discontinuation of treatment. One patient died, probably because detoxication was discontinued too soon after the thyroid hormone levels had normalized. Plasma exchange by using albumin (120 g/4,000 ml = 30 g/l) as replacement fluid is superior to that by using fresh-frozen plasma (2,000 ml/4,000 ml), since less thyroxine is administered (19 vs. 160 nmol).

Amelioration of postischemic acute renal failure by prostacyclin analogue (iloprost): long-term studies with chronically instrumented conscious dogs.

The potential therapeutic value of the chemically stable carbacyclin analogue iloprost on the course of postischemic acute renal failure was studied in six conscious chronically instrumented dogs and compared with five controls. Immediately after temporary ischemia (180-min cessation of blood flow by inflation of a pneumatic cuff), the investigational group PC received a continuous intraaortal infusion of iloprost (50 ng X min-1 X kg-1) over a period of seven days, whereas the control group C received 0.9% saline. The glomerular filtration rate [( 51Cr]EDTA clearance, endogenous creatinine clearance) was less decreased in the prostacyclin analogue group than in the control group [3rd day, 18 +/- 2.5 vs. 12 +/- 1 ml X min-1 (p less than 0.05); 7th day, 23 +/- 3 vs. 12 +/- 2 ml X min-1 (p less than 0.05)]. On day 1, renal blood flow (electromagnetic flow probe) was markedly lower in the control group (129 +/- 29 ml X min-1) than in the PC group (212 +/- 29 ml X min-1; p less than 0.05), even exceeding baseline levels in the latter group. Accordingly, the excessive rise in renal vascular resistance in the control group (+136%) was abolished in the PC group (-32%; p less than 0.01). Nitrogen retention was also markedly improved. Osmolar clearance was markedly lower in the control group (0.58 +/- 0.2 ml X min-1) than in the PC group (1.41 +/- 0.17 ml X min-1; p less than 0.05). It is suggested that the beneficial effect of iloprost is mediated by preservation of renal perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring dialysis efficacy by comparing delivered and predicted Kt/V.

INTRODUCTION: In Europe, especially in Germany, little is currently known about the relationship between delivered and predicted haemodialysis doses for patients on maintenance haemodialysis. We compared delivered and predicted Kt/V in patients of an outpatient dialysis centre in Berlin by calculating the ratio of delivered and predicted Kt/V, resulting in the efficacy quotient, QE. Moreover, we studied the influence of technical and anthropometric parameters on both delivered Kt/V and QE under routine clinical conditions. METHODS: Blood samples were taken after the long interval in a thrice-weekly regimen before and 10 min after ultrafiltration and 100 ml/min slow-pump method. Delivered Kt/V was computed using the Daugirdas III formula. Predicted Kt/V was estimated from the dialysis filter urea clearance given by the manufacturer, treatment time and the total body water (V) computed by the Watson formula and was corrected for real blood flow. As and when appropriate, bivariate and multivariate regression analyses were used to make comparisons. RESULTS: The mean quotient (QE) between delivered and predicted Kt/V was 1.02+/-0.20. Mean delivered Kt/V in 377 treatments of 128 patients was 1.28+/-0.27. Delivered Kt/V and QE were positively associated (P<0.001). QE was significantly associated with post-HD urea, body mass index (BMI) and sex, but not with session time. Significant positive predictors for delivered Kt/V were post-dialysis urea, sex, session time, blood flow and kind of vascular access. BMI was inversely related to delivered Kt/V. DISCUSSION: In this study, the relationship between delivered and predicted Kt/V (QE) was reproducible and close to the ideal value of 1.0. In contrast to delivered Kt/V, QE was not influenced by session time, and positively by BMI. Since QE gives a valid measure of technical dialysis efficacy we suggest the use of this parameter in addition to delivered Kt/V to monitor HD adequacy in clinical routine more comprehensively.

Computational analysis of blood volume curves and risk of intradialytic morbid events in hemodialysis.

BACKGROUND: Blood volume (BV) curves have been used to prevent intradialytic morbid events (IMEs) caused by hypotensive episodes in hemodialysis treatment. However, no standardized parameter is available to describe BV dynamics and to enable online interference with ultrafiltration rates in unselected patients. Moreover, only time-dependent BV reduction and absolute hematocrit threshold, but not BV variability, have been suggested as markers of pending hypotension. The present study therefore deals with a computer-aided analysis of indices characterizing both BV reduction per time and BV variability in treatments of nonselected maintenance hemodialysis patients. METHODS: The methodology uses indices obtained by mathematical analysis of BV curves and was designed to potentially enable automatic interference with ultrafiltration. RESULTS: In 46 out of 380 treatments (12.1%), IMEs occurred. In these treatments, the indices for long- and short-term variability and slope of the curves were significantly lower than in treatments without IMEs. Moreover, the last 10 minutes before an IME were characterized by additionally decreased variability and slope. In a risk analysis of long-term variability and IMEs, we established an index below 16 to be associated with the highest risk of IMEs. CONCLUSIONS: Using these kind of index thresholds and online analysis of BV curves, automatic management of ultrafiltration by BV dynamics could be a promising concept to avoid intradialytic morbidity.