Beta-trace protein-based equations for calculation of GFR in renal transplant recipients.

Recently, we showed that serum beta-trace protein (BTP) is an alternative marker of glomerular filtration rate (GFR) in renal transplant recipients (RTR). We have now developed three BTP-based GFR formulae derived by multiple regression analyses from the patients who had participated in that study. Currently, we validated the diagnostic performance of these BTP-formulae in 102 consecutive RTR who underwent a technetium diethylenetriamine pentaacetic acid (DTPA) clearance for GFR measurement in comparison to the re-expressed Modification of Diet in Renal Disease (MDRD) equation and a recently proposed BTP-based equation (referred to as 'White equation'). The best-performing BTP formula was found to be: GFR = 89.85 x BTP(-0.5541)x urea(-0.3018). This equation estimated true GFR virtually without bias (+0.43 mL/min/1.73 m(2), not significant [NS]), while a small, but significant, overestimation was seen for the MDRD formula (+3.43 mL/min/1.73 m(2), p = 0.003). Precision and accuracies within 50% of true GFR (93.1% and 88.2%, respectively) tended to be higher for the BTP formula, but the differences did not reach significance. The White equation overestimated the true GFR by 9.43 mL/min/1.73 m(2)(p = 0.001), and was inferior with respect to precision and 50% accuracy (79.4%). BTP-based GFR calculations are reliable, and may serve as an alternative to the re-expressed MDRD equation.

Cystatin C-based calculation of glomerular filtration rate in kidney transplant recipients.

Cystatin C (Cys C) has been shown to be an alternative marker of renal function. However, estimation of the glomerular filtration rate (GFR) based on Cys C has received little attention. Recently, several Cys C-based equations were developed in different patient cohorts. To date, the benefit of a Cys C-based GFR calculation in patients after renal transplantation (RTx) remains to be elucidated. We compared the diagnostic accuracy of three Cys C-based formulae (Larsson, Hoek, Filler which used an immunonephelometric method) with the results of the Modification of Diet in Renal Disease (MDRD) formula. GFR was measured by means of technetium-diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) clearance in 108 consecutive patients after RTx. Correlation coefficients of all calculated GFR estimates with the true GFR were high but did not differ significantly from one another (0.83-0.87). The MDRD and Filler equations overestimated GFR significantly, whereas the Larsson equation significantly underestimated GFR. Bias of the Hoek formula was negligible. Precision of the Hoek (8.9 ml/min/1.73 m(2)) and Larsson equations (9.6 ml/min/1.73 m(2)) were significantly better than MDRD equations (11.4 ml/min/1.73 m(2); P< or =0.035 each). Accuracy within 30% of real GFR was 67.0 and 65.1% for the MDRD and Filler formulae, and 77.1% for the Larsson and Hoek formulae, respectively. Accuracy within 50% of true GFR for the Hoek formula (97.2%) was better than for the MDRD equations (85.3%). Cys C-based formulae may provide a better diagnostic performance than creatinine-based equations in GFR calculation after RTx.

Calculation of glomerular filtration rate based on cystatin C in cirrhotic patients.

BACKGROUND: Plasma creatinine and creatinine clearance are of limited value for the estimation of renal function in cirrhotics. In these patients, cystatin C (Cys C) has been proposed as an alternative marker of glomerular filtration rate (GFR) and Cys C-based equations for calculation of GFR have been developed in non-cirrhotic patient cohorts. METHODS: We retrospectively analyzed correlation, bias, precision and accuracy of two Cys C-based formulae (Larsson and Hoek) for GFR estimation in comparison with two creatinine-based equations (Cockroft & Gault and MDRD). The Cys C was determined by an immunonephelometric method. The GFR was measured by means of inulin clearance in 44 consecutive patients with liver cirrhosis. RESULTS: On average, inulin clearance was 28.3 (95% CI: 29.2-41.3 ml/min/1.73 m2). Creatinine as well as Cys C-based equations overestimated the true GFR by 105-154%. However, Cys C-based equations showed significantly lower bias and higher precision than the creatinine-based formulae. Correlation and accuracy tended to be better with the Hoek and Larsson equation than with the Cockroft & Gault or MDRD formulae. Hoek and Larsson equations showed a similar diagnostic performance in all statistical procedures. CONCLUSION: Our data suggest a significant improvement of GFR estimation in liver cirrhotics by means of the Cys C-based Hoek and Larsson formulae. However, all estimates remain a crude approximation of true GFR and thus cannot replace gold standard methods.

Renal anemia aggravated by long-term parvovirus B19 and cytomegalovirus infection in a renal transplant patient: case report and evaluation of B19 seroprevalence in dialysis patients.

Due to viral replication in erythroid precursor cells, severe anemia represents a major complication of B19 infection. However, cytomegalovirus (CMV) is the leading cause of virus-induced complications with a significant impact on graft outcome of renal transplant patients. Herein, we present a long-term B19 infection in a 45-year-old female renal transplant patient, which aggravated the renal anemia associated with a concomitant CMV infection. Since no data were available on the seroprevalence of this virus in pretransplant patients, we determined the B19 serostatus of 90 dialyzed pretransplant adult subjects.

Intravenous treatment of hyperhomocysteinemia in patients on chronic hemodialysis--a pilot study.

BACKGROUND: Treatment of hyperhomocysteinemia in patients with end-stage renal disease (ESRD) can be performed with the oral application of vitamins. However, this therapy rarely normalizes total homocysteine (tHcy) levels. Frequently, a rebound is observed after the end of treatment. Currently, no data are available about intravenous combination therapy with folic acid, pyridoxine (B6), and cyanocobalamin (B12). METHODS: We conducted a prospective pilot study comprising 13 patients on chronic hemodialysis treatment (63.7+/-4.9 years; 6 female, 7 male) for 27 weeks. The patients received 10 mg folic acid and 100 mg pyridoxine intravenously (IV) after each dialysis plus 1000 microg vitamin B12 IV once a week for 9 weeks. Between weeks 10 and 18 the patients received 10 mg folic acid, 100 mg vitamin B6 once a week, and 1000 microg vitamin B12 bimonthly IV. RESULTS: The therapy regimen decreased tHcy concentration (baseline: 30.5+/-2.2 micromol/L) significantly to 17.4+/-1.2 micromol/L, 15.6+/-1.0 micromol/L, and 16.4+/-0.1 micromol/L after 3, 6, and 9 weeks, respectively (p<0.01 vs. baseline concentration). The maximum reduction (-47.5+/-3.3%) of tHcy concentration was measured after 6 weeks of therapy. During the following maintenance therapy, tHcy-levels did not increase and no rebound of tHcy was detected during follow-up (week 27:16.5+/-1.97 micromol/L). CONCLUSION: The concept of a short, high-dose induction therapy with intravenous folic acid, pyridoxine, cyanocobalamin, and a subsequent low-dose maintenance regimen is effective in the treatment of hyperhomocysteinemia in patients with ESRD.

Cystatin C as an endogenous marker of glomerular filtration rate in renal transplant patients.

BACKGROUND: Serum creatinine is the most common endogenous marker used to estimate the glomerular filtration rate (GFR). However, creatinine depends considerably on muscle mass, and its tubular secretion increases, especially in chronic renal failure. Cystatin C is a 13-kD protease inhibitor which is produced by all nucleated cells and is independent of muscle mass and sex. Cystatin C is eliminated by glomerular filtration and metabolized by proximal tubular cells. Its measurement has been proposed as an alternative and more sensitive marker of GFR than creatinine in patients with slight to moderately decreased GFR. METHODS: We investigated serum cystatin C levels in comparison with creatinine as a single measurement for estimation of GFR in 173 patients after renal transplantation. GFR was calculated as creatinine clearance according to standard equations. RESULTS: Serum creatinine correlated well with cystatin C (r = 0.84; p < 0.0001). No significant differences were obtained for the comparison of the linear correlation of 1/creatinine with creatinine clearance (r = 0.77; p < 0.0001) and for the linear correlation of 1/cystatin C with creatinine clearance (r = 0.73; p < 0.0001). However, we found a significant advantage of cystatin C in detecting a clinical relevant reduction of kidney function (GFR <70 ml/min; p = 0.0047, McNemar test). CONCLUSION: Cystatin C is an alternative marker for the assessment of GFR in renal allograft recipients that may be superior to creatinine.

Long term outcome after transjugular intrahepatic portosystemic stent-shunt in non-transplant cirrhotics with hepatorenal syndrome: a phase II study.

BACKGROUND: Recent small studies on hepatorenal syndrome (HRS) indicate some clinical benefit after transjugular intrahepatic portosystemic stent-shunt (TIPS) but sufficient long term data are lacking. AIM: We studied prospectively feasibility, safety, and long term survival after TIPS in 41 non-transplantable cirrhotics with HRS (phase II study). PATIENTS AND METHODS: HRS was diagnosed using current criteria (severe (type I) HRS, n=21; moderate (type II) HRS, n=20). Thirty one patients (14 type I, 17 type II) received TIPS (8-10 mm) while advanced liver failure excluded shunting in 10. During follow up (median 24 months) we analysed renal function and survival (Kaplan-Meier). RESULTS: TIPS markedly reduced the portal pressure gradient (21 (5) to 13 (4) mm Hg (mean (SD)); p<0.001) with one procedure related death (3.2%). Renal function deteriorated without TIPS but improved (p<0.001) within two weeks after TIPS (creatinine clearance 18 (15) to 48 (42) ml/min; sodium excretion 9 (16) to 77 (78) mmol/24 hours) and stabilised thereafter. Following TIPS, three, six, 12, and 18 month survival rates were 81%, 71%, 48%, and 35%, respectively. As only 10% of non-shunted patients survived three months, total survival rates were 63%, 56%, 39%, and 29%, respectively. Multivariate Cox regression analysis revealed bilirubin (p<0.001) and HRS type (p<0.05) as independent survival predictors after TIPS. CONCLUSIONS: TIPS provides long term renal function and probably survival benefits in the majority of non-transplantable cirrhotics with HRS. These data warrant controlled trials evaluating TIPS in the management of HRS.

[The Churg-Strauss syndrome with cerebral seizures and terminal kidney failure]. / Churg-Strauss-Syndrom mit zerebralen Krampfanfällen und terminaler Niereninsuffizienz.

HISTORY AND CLINICAL FINDINGS: A 67-year-old man with known bronchial asthma was admitted to hospital because of deteriorating general state of health, fever, progressive renal failure and confusional states. INVESTIGATIONS: Erythrocyte sedimentation rate was 70/95 mm and the concentration of C-reactive protein raised to 30 mg/dl. WBC count was 19,000/microliter with 39% eosinophilia. Anticytoplasmatic antibodies (cANCA) had a high titre (1:160). On admission the creatinine level was 5.6 mg/dl. Renal biopsy indicated marked glomerular and tubulo-interstitial scarring. Chest radiograms showed transient pulmonary infiltrates. Churg-Strauss syndrome (CSS) was diagnosed on the basis of the clinical and biochemical findings. TREATMENT AND COURSE: Haemodialysis was instituted to counteract the renal failure with water retention. Inflammatory parameters and clinical symptoms rapidly responded to administration of corticosteroids (prednisolone, initially 250 mg/d for 3 days, then 150 mg/d for 5 days followed by slowly decreasing doses). Two weeks after starting prednisolone he had secondary generalised seizures. Magnetic resonance imaging (MRI) of the skull demonstrated marked hyperintense focal changes which in their pattern were characteristic of cerebral vasculitis. As a steroid-refractory condition had to be assumed, cyclophosphamide was also given (100 mg/d). Within 6 weeks the clinical symptoms gradually regressed and the MRI changes became practically normal. CONCLUSION: Early combined immunotherapy should be given if CSS runs a complicated course, rather than the usually recommended corticosteroid monotherapy.

Successful induction and consolidation therapy of acute myeloid leukaemia in a renal allograft recipient.

Immunosuppressed organ transplant recipients have a markedly increased risk of neoplasia. Among these malignancies acute myeloid leukaemia (AML) is rare. However, until now no case of successful chemotherapy has been reported. We present a 39-year-old male patient who developed AML (FAB M4 Eo) 4 years after renal transplantation and achieved a stable complete remission after induction therapy with standard dose cytarabine and daunorubicin. Remission duration is now 11 months. At present the transplant is functioning well after two additional courses of consolidation chemotherapy with high-dose cytarabine combined with mitoxantrone and idarubicine respectively. Cyclosporin A was given during all cycles of chemotherapy. We conclude that intensive chemotherapy in patients with AML following renal transplantation in good performance status is feasible.

Tumour induction as a consequence of immunosuppression after renal transplantation.

Immunosuppressed recipients of organ transplants have a higher incidence of carcinoma than the general population. A retrospective analysis was made at the Department of Urology of Bonn University, investigating 236 renal allograft recipients as to the incidence of neoplasms before and after transplantation. Eleven patients developed malignant tumours after transplantation. In 4 out of these 11 patients, case history showed pre-existing malignancies. Two of the 4 patients developed a second tumour, while the other two had tumour progression (latency period 21-77 months). Three of the 4 patients died of their tumours 21, 42 and 77 months after transplantation, whereas one female patient is still alive and free of neoplasms 32 months after transplantation. In 7 out of these 11 patients de novo tumours were diagnosed (latency period 3-88 months). All of them are still alive (NED between 15 and 85 months), six of them with good transplant function. There was no difference to be seen in the incidence of malignancies between kidneys supplied by Eurotransplant (n = 40) and ABO compatible kidneys from our own donors (n = 196). The higher incidence rate of neoplasms in transplant recipients requires high standards in preventive measures. Any suspicious change that may occur in the course of a thorough follow-up of transplant recipients must be removed and examined histologically. Patients with previous malignant diseases must be payed special attention, since they frequently tend to develop another malignant tumour and progression of existing tumours, respectively. As far as immunosuppression is concerned, therapeutic guidelines for the treatment of transplant recipients do not differ from those set up for patients on haemodialysis. Since immunosuppression with increased rates of tumour incidence can also be observed in dialysis patients, the mere fact of increased incidence of neoplasms cannot be taken as an argument against transplantation. With a more or less equal risk of tumour incidence the crucial factor should be the higher quality of life for transplant recipients.