Fred Nieman

No advantage of flow cytometry crossmatch over complement-dependent cytotoxicity in immunologically well-documented renal allograft recipients.

The effect of flow cytometry crossmatches on clinical outcome was studied retrospectively in two groups of immunologically well-documented patients who had received transplants with a negative complement-dependent cytotoxicity crossmatch. The first group consisted of 114 consecutive renal allograft recipients, and the second group consisted of 76 immunologically at-risk recipients. Flow cytometry crossmatches were performed with current and historic sera. In group 1, positive flow cytometry (FC) crossmatches were shown in 15/114 (13%) recipients. Rejection occurred in 8/15 (53%) FC-positive versus 41/99 (41%) FC-negative recipients. The 1-year graft survival rate was 80% for FC-positive patients and 87% for FC-negative patients. Sixty-seven patients were nonsensitized patients; 4 of them had a positive FC crossmatch but no rejection episodes, graft loss, or patient loss. Of 47 retransplanted and/or sensitized recipients, 11 had a positive FC crossmatch. Rejection treatment was needed in 8/11 (73%) FC-positive patients compared with 19/36 (53%) FC-negative patients. Their 1-year graft survival rates were 73% and 81%. None of these differences reached statistical significance. Group 2 consisted of 76 at-risk recipients; 37 were retransplant patients and 39 were sensitized first-transplant patients. Twenty-one (28%) patients showed a positive FC crossmatch. Rejection episodes did not differ between the FC-positive (48%) and FC-negative patients (46%). There was no difference in 1-year graft survival rate (76% vs. 80%) or in 1-year patient survival rate (100% vs. 95%). We conclude that FC crossmatches in our patient group are not superior to the classical complement-dependent cytotoxicity crossmatches with regard to clinical outcome. On the contrary, transplantation with a mandatory negative FC crossmatch would have excluded 28% of the recipients from transplantation, who in fact are doing well.

Similarities in skeletal muscle strength and exercise capacity between renal transplant and hemodialysis patients

Exercise intolerance is common in hemodialysis (HD) and renal transplant (RTx) patients. Aim of the study was to assess to what extent exercise capacity and skeletal muscle strength of RTx patients differ from HD patients and healthy controls and to elucidate potential determinants of exercise capacity in RTx patients. Exercise capacity, muscle strength, lean body mass (LBM) and physical activity level (PAL) were measured by cycle‐ergometry, isokinetic dynamometry, DEXA and Baecke Questionnaire, respectively, in 35 RTx, 16 HD and 21 controls. VO2peak and muscle strength of the RTx patients were significantly lower compared to controls (p < 0.01), but not different compared to HD patients. In RTx patients, strength (p < 0.001), PAL (p = 0.001) and age (p = 0.045) were significant predictors of VO2peak. Muscle strength was related to LBM (p = 0.001) and age (p = 0.001), whereas gender (p < 0.001) and renal function (p = 0.01) turned out to be significant predictors of LBM. No effects of corticosteroids were observed. Exercise capacity and muscle strength seem equally reduced in RTx and HD patients compared to controls. In RTx patients, muscle strength and PAL are highly related to exercise capacity. Renal function appears to be a significant predictor of LBM, and through the LBM, of muscle strength and exercise capacity.

Donor-specific antibodies after transplantation by flow cytometry: relative change in fluorescence ratio most sensitive risk factor for graft survival.

BACKGROUND There is no consensus on the role of donor-directed antibodies after renal transplantation detected by complement-dependent cytotoxicity (CDC) or by flow cytometry (FC). METHODS Therefore, antibody formation was studied by FC and correlated with clinical course in a group of patients who received transplants between 1983 and 1993. All had a negative current CDC crossmatch and were treated with cyclosporine. Current and posttransplant sera from 143 donor-recipient combinations were studied retrospectively. Antibodies were considered present in FC if the fluorescence ratio between serum and negative control was > 2.65. RESULTS Of 143 patients, 17 (11.9%) were found to be positive in the posttransplant FC crossmatch and 126 (88.1%) were negative. Of the positive patients, 3 were already positive in the current FC crossmatch, whereas 14 demonstrated a positive posttransplant FC crossmatch after a negative current FC crossmatch. It was noteworthy that, from 16 patients with a positive current FC crossmatch, 13 turned negative in the posttransplant crossmatch. In 113 recipients (79%), both pre- and posttransplant FC crossmatches were negative. The development of a positive FC crossmatch after transplantation was a significant risk factor for graft survival in Cox regression analysis (P = 0.01). The results were also studied as relative change in fluorescence ratio (RCFR). RCFR was determined by classifying the recipients in quartiles according to their change in flow cytometric value from current to posttransplant serum. Quartiles were defined as follows: quartile 1, decrease > 10%; quartile 2, decrease 0-10%; quartile 3, increase > 0-30%; and quartile 4, increase > 30%. RCFR proved to be the only significant risk factor for graft survival (odds ratio for quartile 4 vs. quartile 1, 3.27; P < 0.02). More rejections were shown for increasing quartile numbers (P < 0.001). CONCLUSIONS Classification of patients by RCFR detected more patients with unfavorable clinical outcome (25% vs. 11%) than by FC crossmatch.

Efficacy of Physical Therapeutic Modalities in Women with Proven Bladder Overactivity

OBJECTIVE To assess the efficacy of physiotherapeutic treatment modalities in women with proven bladder overactivity. METHODS One hundred and twelve women received ambulatory urodynamics. Based on both urodynamic variables of ambulatory cystometry (ACM) and the micturition diary, the Detrusor Activity Index (DAI) for each patient was calculated. After randomization, 68 women with a DAI> or =0.50 were defined as having proven bladder overactivity. In a single blinded RCT patients were randomized over four treatment groups, i.e. lower urinary tract exercises (LUTE); office- and home-based functional electrostimulation (FES); office-based FES and LUTE; no treatment. Patients treated received nine treatment sessions, once weekly. The primary outcome variable was the DAI, measured before randomization and, as soon as possible within a maximum of 14 days after the end of the study period. RESULTS Intention to treat analysis in the group of 68 patients showed a statistically significant decrease of DAI-scores in the FES group (p=0.032) in comparison with no treatment, while this decrease was not statistically significant in the LUTE group (p=0.105) and the LUTE+FES group (p=0.672). CONCLUSIONS Our conclusion is that, based on the DAI, in the homogeneous set of 68 patients, only FES seemed to be effective.

The functional, metabolic, and anabolic responses to exercise training in renal transplant and hemodialysis patients.

Background. Exercise intolerance is common in hemodialysis (HD) and renal transplant (RTx) patients and is related to muscle weakness. Its pathogenesis may vary between these groups leading to a different response to exercise. The aim of the study was to compare intrinsic muscular parameters between HD and RTx patients and controls, and to assess the response to exercise training on exercise capacity and muscular structure and function in these groups. Methods. Quadriceps function (isokinetic dynamometry), body composition (dual-energy x-ray absorptiometry), and vastus lateralis muscle biopsies were analyzed before and after a 12-week lasting training-program in 35 RTx patients, 16 HD patients, and 21 healthy controls. Results. At baseline, myosin heavy chain (MyHC) isoform composition and enzyme activities were not different between the groups. VO2peak and muscle strength improved significantly and comparably over the training-period in RTx, HD patients and controls (ptime<0.05). The proportion of MyHC type I isoforms decreased (ptime<0.001) and type IIa MyHC isoforms increased (ptime<0.05). The 3-hydroxyacyl-CoA-dehydrogenase activity increased (ptime=0.052). Intrinsic muscular changes were not significantly different between groups. In the HD group, changes in lean body mass were significantly related to changes in muscle insulin-like growth factor (IGF)-II and IGF binding protein-3. Conclusions. Abnormalities in metabolic enzyme activities or muscle fiber redistribution do not appear to be involved in muscle dysfunction in RTx and HD patients. Exercise training has comparable beneficial effects on functional and intrinsic muscular parameters in RTx patients, HD patients, and controls. In HD patients, the anabolic response to exercise training is related to changes in the muscle IGF system.

Predictive factors for nocturia in elderly men: a cross-sectional study in 21 general practices

To measure the prevalence of nocturia in general practice and to determine which factors are associated with nocturia.

Sacral Neuromodulation Therapy: A Promising Treatment for Adolescents With Refractory Functional Constipation

BACKGROUND: Sacral neuromodulation therapy has been successfully applied in adult patients with urinary and fecal incontinence and in adults with constipation not responding to intensive conservative treatment. No data, however, are available on sacral neuromodulation therapy as a treatment option in adolescents with refractory functional constipation. OBJECTIVES: This study aimed to describe the short-term results of sacral neuromodulation in adolescents with chronic functional constipation refractory to intensive conservative treatment. DESIGN: This is a retrospective review. SETTING: This study took place at the Department of Surgery, Maastricht University Medical Centre, The Netherlands. PATIENTS: Thirteen patients (all girls, age 10–18 years) with functional constipation according to the ROME III criteria not responding to intensive oral and rectal laxative treatment were assigned for sacral neuromodulation. MAIN OUTCOME MEASURES: When improvement of symptoms was observed during the testing phase, a permanent stimulator was implanted. Patients were prospectively followed up to at least 6 months after implantation of the permanent stimulator by interviews, bowel diaries, and Cleveland Clinic constipation score. Improvement was defined as spontaneous defecation ≥2 times a week. RESULTS: At presentation, none of the patients had spontaneous defecation or felt the urge to defecate. All patients had severe abdominal pain. Regular school absenteeism was present in 10 patients. After the testing phase, all but 2 patients had spontaneous defecation ≥2 times a week with a reduction in abdominal pain. After implantation, 11 (of 12) had a normal spontaneous defecation pattern of ≥2 times a week without medication, felt the urge to defecate, and perceived less abdominal pain without relapse of symptoms until 6 months after implantation. The average Cleveland Clinic constipation score decreased from 20.9 to 8.4. One lead revision and 2 pacemaker relocations were necessary. LIMITATIONS: This study is limited by its small sample size, single-institution bias, and retrospective nature. CONCLUSION: Sacral neuromodulation appears to be a promising new treatment option in adolescents with refractory functional constipation not responding to intensive conservative therapy. Larger randomized studies with long-term follow-up are required.

PNE versus 1st stage tined lead procedure: a direct comparison to select the most sensitive test method to identify patients suitable for sacral neuromodulation therapy.

To compare the patients response rate to the Percutaneous Nerve Evaluation test (PNE) and the 1st stage tined‐lead placement test (FSTLP) for sacral neuromodulation therapy (SNM).

Satisfaction and Patient Experience With Sacral Neuromodulation: Results of a Single Center Sample Survey

PURPOSE We systematically assessed long-term satisfaction and patient experience with sacral nerve modulation therapy. MATERIALS AND METHODS All patients who received sacral neuromodulation between 1990 and 2007 at our center and who still had the implant were included in the survey. All received a postal questionnaire regarding satisfaction and experiences with the system, such as side effects, complications, burden, impact on sexuality and defecation changes. RESULTS Of the 275 questionnaires sent 207 were returned for a 75% response rate. The population was 83% female. Overall treatment was done for overactive bladder syndrome, nonobstructive urinary retention, combined overactive bladder and retention, and pelvic pain in 55%, 24%, 20% and 1% of patients, respectively. Overall satisfaction with sacral neuromodulation was high at 90%. No correlations were found between the satisfaction rate, and pretreatment age, gender, complaint type, sexual dysfunction or therapy duration. However, 56% of patients reported side effects, such as pain at the internal nerve stimulator site and due to stimulation. However, 89% of these patients did not seek further therapy. Of patients with additional defecation problems 47% experienced relief of complaints. CONCLUSIONS This study shows a high satisfaction rate in patients with sacral neuromodulation. There was no relation between patient age, complaint type, therapy duration or side effects and the satisfaction rate. The number of side effects was limited but further analysis in prospective cohorts should identify patients who are likely to have side effects or stop sacral neuromodulation treatment.

Early Loss of Peritubular Capillaries after Kidney Transplantation

Inflammation, interstitial fibrosis (IF), and tubular atrophy (TA) precede chronic transplant dysfunction, which is a major cause of renal allograft loss. There is an association between IF/TA and loss of peritubular capillaries (PTCs) in advanced renal disease, but whether PTC loss occurs in an early stage of chronic transplant dysfunction is unknown. Here, we studied PTC number, IF/TA, inflammation, and renal function in 48 patients who underwent protocol biopsies. Compared with before transplantation, there was a statistically significant loss of PTCs by 3 months after transplantation. Fewer PTCs in the 3-month biopsy correlated with high IF/TA and inflammation scores and predicted lower renal function at 1 year. Predictors of PTC loss during the first 3 months after transplantation included donor type, rejection, donor age, and the number of PTCs at the time of implantation. In conclusion, PTC loss occurs during the first 3 months after renal transplantation, associates with increased IF and TA, and predicts reduced renal function.