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L B Hilbrands

Publications and source records attributed to L B Hilbrands.

At least 19 recordsLinked to original sources
PubMed2006

Following anti-CD25 treatment, a functional CD4+CD25+ regulatory T-cell pool is present in renal transplant recipients.

Daclizumab, a humanized antibody directed against the alpha-chain of the interleukin-2 receptor (CD25), has shown efficacy in the prevention of acute rejection following organ transplantation. However, anti-CD25 therapy can be expected to affect not only alloreactive effector T cells, but also CD4(+)CD25(+) regulatory T (Treg) cells that are shown to play an important role in the induction of transplantation tolerance. Therefore, the size and function of the Treg pool in human renal allograft recipients after single-dose daclizumab administration was investigated in this study. Approximately 8 weeks after administration, daclizumab was cleared from the circulation and the Treg population then present appeared not different from that observed before transplantation. Functional analysis revealed that the Treg possessed a normal capacity to suppress mixed lymphocyte reactions in vitro. These data indicate that after daclizumab therapy a Treg population, normal in number and function, is present in the peripheral blood of renal transplant recipients.

Adult↗
PubMed2006

Diagnostic approach in patients with asymptomatic haematuria: efficient or not?

Many patients with asymptomatic haematuria are primarily referred to urological examination. To analyse the efficiency of this strategy, we investigated the diagnostic process in 134 patients with asymptomatic haematuria (91 macroscopic and 43 microscopic) who were referred to our urology department. The frequency of diagnostic procedures was urine culture: 91%, cystoscopy: 87%, intravenous urography: 86%, ultrasound: 73%, examination of urinary sediment: 20%. In 70 patients (52%), a urological diagnosis was made. In the remaining 64 patients, the urinary sediment was examined for the presence of dysmorphic erythrocytes and erythrocyte casts in 17 patients (27%). Signs of glomerular haematuria were found in nine of them (53%). The diagnostic strategy in these patients with asymptomatic haematuria was not discordant from several published algorithms but appeared neither efficacious nor efficient. We estimate that when examination of the urinary sediment would have been performed at the start of work-up, 25% of patients could have spared from extensive urological investigation.

Adult↗
PubMed2006

Sirolimus-associated heavy proteinuria in a renal transplant recipient: evidence for a tubular mechanism.

Sirolimus is a new and potent immunosuppressive agent. Recently, increased proteinuria has been recognized as an important complication. However, the mechanism thereof has remained unclear. We describe a patient who received sirolimus as standard therapy after living donor kidney transplantation. Within 10 days the patient developed a severe proteinuria that disappeared completely after substituting tacrolimus for sirolimus. Renal biopsy disclosed normal glomeruli even without effacement of the podocytic foot processes. Using FITC labeled anti-albumin antibodies we noted complete absence of albumin in the proximal tubules, whereas an abundant albumin staining was observed in a control patient with a comparable level of proteinuria due to a recurrence of focal segmental glomerulosclerosis after transplantation. Our data suggest that sirolimus can induce severe proteinuria, and that reduced tubular protein reabsorption contributes to the protein loss.

Biopsy↗
PubMed2005

Idiopathic focal segmental glomerulosclerosis: a favourable prognosis in untreated patients?

BACKGROUND: Patients with focal segmental glomerulosclerosis (FSGS) are considered to have a poor prognosis and spontaneous remissions are seldom reported. However, FSGS is not a single disease entity. Our aim was to describe the clinical course in initially untreated patients with recently diagnosed idiopathic FSGS. METHODS: This was a retrospective study of patients with a diagnosis of FSGS by histology, who fulfilled the following criteria: proteinuria >3.5 g/day, normal renal function, duration of proteinuria or hypertension of less than one year, normal-sized kidneys, no underlying renal disease, and a negative family history. Renal biopsies were reviewed without knowledge of the clinical course. RESULTS: Twenty patients (13 male, 7 female) fulfilled the study criteria. Median age was 49.3 (range 21.8 to 73.0) years, serum creatinine 90 +/- 20 micromol/l, proteinuria 10.0 +/- 5.5 g/day and serum albumin 24 +/- 6 g/l. After a median follow-up of 9.4 (2.1-18.6) years, 13 patients (65%) were in remission of proteinuria. Renal function deterioration occurred in seven patients, and prompted treatment in four of them. The ten-year death-censored renal survival was 89%. Renal function deterioration and remission rate could be predicted by selectivity index, serum albumin at three months after renal biopsy and the percentage of glomeruli with segmental sclerosis. CONCLUSION: Focal glomerulosclerosis is not a single disease. Case definition using strict clinical criteria identifies a subgroup of patients with idiopathic FSGS who have a good prognosis. In the majority of these patients immunosuppressive therapy is not warranted.

Adult↗
PubMed2004

The (fixed) urinary sediment, a simple and useful diagnostic tool in patients with haematuria.

Examination of the urinary sediment is a simple and indispensable tool in the diagnostic approach to patients with asymptomatic haematuria. Various glomerular and nonglomerular diseases can cause haematuria. A well-trained expert can distinguish between these two forms of haematuria by examining the urinary sediment under a simple light microscope. In glomerular haematuria, dysmorphic erythrocytes and erythrocyte casts are found, whereas in nonglomerular haematuria the erythrocytes are monomorphic and erythrocyte casts are absent. However, few people have sufficient expertise in the examination of the urinary sediment, and consequently this investigation is performed far too seldom. A few years ago, a simple method of fixation of the urinary sediment became available. Fixed specimens can be stored at room temperature for at least two weeks, which enables the sending of a fixed specimen to an expert examiner by regular mail. In this way, the urinary sediment can more frequently be used as the initial investigation in the diagnostic route of patients with asymptomatic haematuria.

Algorithms↗
PubMed2001

Elective withdrawal of mycophenolate mofetil in renal transplant recipients treated with mycophenolate mofetil, cyclosporine, and prednisone.

In a retrospective study we investigated the risk of acute rejection after the withdrawal of mycophenolate mofetil (MMF) in 39 adult patients treated with cyclosporine (CyA), prednisone, and MMF for at least 6 months following renal transplantation. After reaching a stable renal graft function, MMF was withdrawn and CyA and prednisone were continued. Preceding the withdrawal of MMF, four patients experienced an acute rejection. During a median follow-up of 38 months after discontinuing MMF, no acute rejection occurred. The mean serum creatinine level did not change during the first 6 months after withdrawal of MMF. We conclude that elective withdrawal of MMF in stable renal transplant recipients at 6 months after transplantation bears no important risk of an occurrence of acute rejection.

Adolescent↗
PubMed2001

Lower urinary tract symptoms after renal transplantation.

PURPOSE: We investigated the prevalence and nature of lower urinary tract symptoms after renal transplantation. In addition, we studied how these symptoms affect the quality of life and whether function of the lower urinary tract before transplantation was related to postoperative occurrence of lower urinary tract symptoms. MATERIALS AND METHODS: Data were gathered by a written questionnaire. The research group consisted of 63 patients who underwent renal transplantation in 1998 at the University Medical Center St Radboud Nijmegen. The control group consisted of 74 patients with nonurological complaints who visited an outpatient clinic at the same university. RESULTS: The most important finding was that patients who underwent renal transplantation needed to void more often than controls, both during the day and at night. After renal transplantation, almost 50% of the patients complained of frequency and 62% nocturia. Patients with a transplant had tended to perceive frequency and nocturia less as problems than those in the control group. CONCLUSIONS: No relation was found between the functioning of the lower urinary tract before transplantation, and occurrence of frequency and nocturia after. The amount of fluid intake at the interview was not related to the occurrence of frequency and nocturia. No abnormalities were found regarding bladder evacuation.

Adolescent↗
PubMed2001

Nadroparin-induced Calcinosis cutis in renal transplant recipients.

Low-molecular-weight heparins are routinely used to prevent deep venous thrombosis following renal transplantation in our department. We report 2 patients who developed tender erythematous subcutaneous nodules with induration, ulceration and necrosis at the site of subcutaneous administration of nadroparin. Both patients were renal transplant recipients with impaired graft function and high serum calcium-phosphate products. The diagnosis calcinosis cutis was confirmed by technetium-99m bone scan and by histological examination of biopsies. Both patients showed spontaneous recovery several weeks after discontinuation of nadroparin. Patients with chronic renal failure and hyperphosphatemia may be predisposed to develop calcinosis cutis. In addition, the role of the calcium content of nadroparin is discussed.

Adult↗
PubMed2000

[Daclizumab and basiliximab: monoclonal mouse-man antibodies with effective immunosuppression without side effects].

Four major double-blind randomized trials in kidney transplant patients have shown that the interleukin-2 receptor (IL-2R alpha) antagonists declizumab or basiliximab, when added to an immunosuppressive regimen consisting of cyclosporin and prednisone, reduce the incidence of acute rejections after kidney transplantation by 30-40%, during the first 6 months. Daclizumab and basiliximab are monoclonal antibodies of which the variable parts are of mouse origin and the other components of human origin. The addition of the interleukin-2 receptor antagonists was not accompanied by extra side effects. Ongoing clinical trials aim at answering the question whether the addition of daclizumab and basiliximab will allow to avoid or decrease the use of more toxic immunosuppressive drugs.

Antibodies, Monoclonal↗
PubMed2000

Type I membranoproliferative glomerulonephritis in a renal allograft: A recurrence induced by a cytomegalovirus infection?

A 40-year-old white woman with end-stage renal disease from idiopathic type I membranoproliferative glomerulonephritis (MPGN) developed proteinuria and renal dysfunction 7 weeks after cadaveric donor renal transplantation. At the same time, a primary cytomegalovirus (CMV) infection was diagnosed. Complement levels were low. A renal biopsy disclosed an acute exudative proliferative glomerulonephritis with influx of polymorphonuclear granulocytes (PMNs), with granular deposits of C3, C1q, IgG, and IgM. The immunofluorescence (IF) and electron microscopy (EM) findings were compatible with an early stage of a type I MPGN. CMV could not be detected in the glomeruli nor elsewhere in the kidney by IF or EM. The patient was treated with ganciclovir. In a renal biopsy 3 weeks later, the exudative lesions had disappeared, and some glomeruli now showed the characteristic lesions of a type I MPGN with an increase of mesangial cells and matrix, and reduplication of the glomerular basement membrane. Over the following period, repeated biopsies were performed. The activity of the glomerular inflammation and immune complex deposits paralleled the waxing and waning of the CMV viral load. After 10.5 months, the graft was removed because of a life-threatening systemic fungal infection. At that time, the CMV infection had cleared, and in the transplantectomy material, the membranoproliferative pattern of injury had disappeared, and in the glomeruli hardly any deposits were found. These data strongly suggest that a primary CMV virus infection can induce an apparent recurrence of type I MPGN.

Adult↗
PubMed2000

The influence of mycophenolate mofetil on the incidence and severity of primary cytomegalovirus infections and disease after renal transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) is increasingly used for immunosuppression after renal transplantation (RTx). The aim of our study was to investigate if the use of MMF has resulted in an increase in the frequency and severity of primary cytomegalovirus (CMV) infections. METHODS: Retrospective study of adult RTx patients who were CMV seronegative and who received a kidney of a CMV seropositive donor in the period 1992-1997 (n=84). Twenty-four of these patients were treated with MMF (in combination with cyclosporin and prednisone; MMF+) and the other 60 were the control group (cyclosporin and prednisone; MMF-). No CMV prophylaxis was given. CMV infection was defined as CMV seroconversion of IgG antibodies. CMV disease was defined as CMV infection and fever in combination with one or more of the following: leukocytopenia, thrombocytopenia, elevated alanine aminotransferase, or histological evidence of tissue invasive disease. RESULTS: The incidence of primary CMV infections was similar in both groups (MMF+, 75%; MMF-, 63%). CMV disease was more frequent in the MMF+ group than in the MMF- group (67 vs 30%, P<0.05). In the patients with CMV disease, the use of MMF did not affect severity of symptoms, frequency of tissue invasive disease, or frequency or duration of treatment with ganciclovir. CONCLUSIONS: Addition of MMF to the immunosuppressive therapy after RTx did not result in an increase of primary CMV infections.However, these CMV infections led more often to CMV disease in patients treated with MMF than in those without MMF.

Adult↗
PubMed1999

Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients.

BACKGROUND: Triple drug treatment consisting of mycophenolate mofetil (MMF), in a standard dose of 2 g daily, combined with cyclosporine (CsA) and prednisone, has become the standard immunosuppressive regimen after kidney transplantation in many centers. The need for therapeutic drug monitoring of mycophenolic acid (MPA) has not yet been established. Several drug interactions with MMF are known. We investigated the influence of CsA withdrawal on MPA trough levels in renal transplant patients. METHODS: Fifty-two patients were treated with 1 g of MMF twice daily, and prednisone and CsA targeted between 125 and 175 ng/ml for 6 months after transplantation. At 6 months after transplantation, 19 patients were randomized for continuation of triple therapy (group A), 19 patients discontinued CsA (group B), and 14 patients discontinued prednisone (group C). We compared 12-hr fasted MPA trough levels at 6 and 9 months after transplantation within and between these groups. RESULTS: MPA trough levels during treatment with CsA, MMF, and prednisone were significantly lower than those during treatment with MMF and prednisone only (group B); median levels were 1.87 mg/L (range: 0.56-5.27) vs. 3.16 mg/L (range: 0.32-7.78), respectively (P=0.002). MPA trough levels in groups A and C did not change between 6 and 9 months after transplantation; group A median levels were 1.87 (range: 0.31-4.32) vs. 1.53 mg/L (range: 0.36-3.70), and group C median levels were 1.62 (range: 0.69-10.34) vs. 1.79 mg/L (range: 0.54-6.00), respectively. At 9 months after transplantation, patients in whom CsA was discontinued had higher MPA trough levels as compared with patients who continued the use of triple therapy (P=0.001) or patients in whom steroids were withdrawn (P=0.014). CONCLUSION: A significant increase of MPA trough levels was found after discontinuation of CsA (6 months after transplantation), resulting in almost a doubling of MPA trough levels at 9 months after transplantation. This resulted in increased MPA levels in patients without CsA as compared to MPA levels in patients continuing triple therapy or discontinuing prednisone.

Cyclosporine↗