Application of improved glomerular filtration rate estimation by a neural network model in patients with neurogenic lower urinary tract dysfunction.

BACKGROUND: Previous studies have indicated that creatinine (Cr)-based glomerular filtration rate (GFR) estimating equations - including the new Chronic Kidney Disease Epidemiology creatinine (CKD-EPIcr) equation without race and the estimated glomerular filtration rate (eGFR) equation developed for the Chinese population - displayed suboptimal performance in patients with neurogenic lower urinary tract dysfunction (NLUTD), which limited their clinical application for detecting changes in GFR levels in all cohorts. OBJECTIVE: To develop a neural network model based on multilayer perceptron (MLP) for evaluating GFR in Chinese NLUTD patients, and compare the diagnostic performance with Cr-based multiple linear regression equations for Chinese and the CKD-EPIcr equation without race. DESIGN: Single-center, cross-sectional study of GFR estimation from serum Cr, demographic data, and clinical characteristics in Chinese patients with NLUTD. PATIENTS: A total of 204 NLUTD patients, from 27 different geographic regions of China, were selected. A random sample of 141 of these subjects was included in the training sample set, and the remaining 63 patients were included in the testing sample set. METHODS: The reference GFR (rGFR) was assessed by the technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) double plasma sample method. A neural network model based on MLP was developed to evaluate GFR in the training sample set, which was then validated in the testing sample set and compared with Cr-based GFR equations. RESULTS: The MLP-based model showed significant performance improvement in evaluating the difference, absolute difference, precision, and accuracy of GFR estimation compared with the Cr-based GFR equations. Additionally, compared with the rGFR, we found that the MLP-based model provided an acceptable level of accuracy (greater than 85%, which was within a 30% deviation from the rGFR). CONCLUSION: The MLP-based model offered significant advantages in estimating GFR in Chinese NLUTD patients, and its application could be suggested in clinical practice.

Comparing Cystatin C- and Creatinine-Estimated Glomerular Filtration Rates in Patients With Thoracic Versus Sacral Motor Levels of Spina Bifida.

OBJECTIVE: Patients with myelomeningocele-type spina bifida are at increased risk of developing kidney disease from neurogenic bladder. Differences between creatinine- and cystatin C-estimated glomerular filtration rates were examined in patients with thoracic versus sacral level myelomeningocele given presumed differences in muscle mass. DESIGN: A retrospective chart review (2005-2018) was performed on 57 adults with myelomeningocele [thoracic n = 44 (77%); sacral n = 13 (23%)]. Concurrently obtained creatinine and cystatin C levels were extracted and calculated creatinine- and cystatin C-estimated glomerular filtration rates were compared. RESULTS: Mean creatinine-estimated glomerular filtration rate was significantly higher for thoracic [140.8 ml/min (SD = 23.9)] versus sacral myelomeningocele [112.0 ml/min (SD = 22.6), P = 0.0003]. There was no difference in cystatin C-estimated glomerular filtration rate between sacral [116.6 ml/min (SD = 23.7)] and thoracic myelomeningocele [124.8 ml/min (SD = 17.9)]. The mean difference between creatinine- and cystatin C-estimated glomerular filtration rates in thoracic myelomeningocele [24.2 ml/min (SD = 16.3)] was significantly greater than in sacral myelomeningocele [-12.8 (SD = 15.7), P < 0.0001]. CONCLUSIONS: There was a significantly higher discrepancy between creatinine- and cystatin C-estimated glomerular filtration rates in thoracic versus sacral motor levels of myelomeningocele. These data suggest that creatinine-estimated glomerular filtration rate may overestimate kidney function in patients with thoracic myelomeningocele. Providers who manage patients with thoracic myelomeningocele should consider monitoring cystatin C to evaluate for underlying renal disease.

[Sensitivity and specificity of urinary and serum neurotrophins in the diagnosis of neurogenic detrusor overactivity in multiple sclerosis].

Lower urinary tract dysfunction is common among neurological patients. Traditionally, the basic method of diagnosis is a complex urodynamic study. In recent years, many studies have focused on the search for new non-invasive diagnostic modalities. In particular, neurotrophins are considered as potential biological markers of a neurogenic bladder. AIM: To estimate the sensitivity and specificity of the serum and urinary nerve growth factor (NGF) and brain neurotrophic factor (BDNF) in MS patients as markers of detrusor overactivity. MATERIALS AND METHODS: The study comprised 20 patients with multiple sclerosis, who complained of voiding problems. The control group consisted of 20 people without neurological diseases, lower urinary tract symptoms and detrusor overactivity estimated by filling cystometry. Apart from standard laboratory tests, diagnostic evaluation included a complex urodynamic study, ultrasound of the urinary tract, cystoscopy, testing serum and urinary NGF and BDNF using the enzyme immunoassay. The diagnostic significance of neurotrophins was evaluated using ROC analysis. RESULTS: According to the ROC analysis, the diagnostic sensitivity and specificity of serum NGF as a marker of detrusor hyperactivity was 57% and 93%, respectively (for serum NGF more or equal 26 pg/ml). The quality of the test according to the expert scale of AUC values was "very good" (AUC=0.806). Detecting NGF in patients urine was less effective. The sensitivity and specificity were 52% and 40%, respectively (for NGF more or equal 6 pg/ml). The quality of the test according to the expert scale of AUC values was "average" (AUC=0.64). The serum BDNF demonstrated high sensitivity (90%) and low specificity (23%), AUC=0.56. The urinary BDNF was more informative, (AUC=0.65). The combination of all four markers provides a sensitivity of 85.7% and a specificity of 66.7% (AUC=0.824). CONCLUSIONS: Testing serum and urinary neurotrophins in patients with multiple sclerosis can be used to diagnose detrusor overactivity. The NGF is a highly specific biomarker, while the BDNF is highly sensitive. Combined testing for serum NGF and BDNF is most informative.

Chronic kidney disease in neurogenic bladder.

AIM: It was believed that neurogenic bladder (NB) might be a risk factor of chronic kidney disease (CKD). However, data are limited regarding the real incidence or risk of CKD in NB. In addition, serum creatinine (sCr), a classical marker of renal function, is not reliable in NB patients because they present muscle wasting due to disuse or denervation. The aim of the study was to estimate the prevalence of CKD in NB patients using serum Cystatin-C. Secondly, we aimed to identify the risk factors for CKD development in NB. METHODS: This was a cross-sectional study in a public hospital, a specialized center for patients who were victims of industrial accidents. Serum Cystatin-C was checked at the regular laboratory test in the structured NB programme of the hospital, and 313 patients were included in the study. RESULTS: The overall prevalence of CKD, defined as estimated glomerular filtration rate (eGFR) <60/mL per 1.73m2 was 8.0% and 22.4%, by sCr-based and Cystain-C-based eGFR, respectively, and was greater than age-matched general population in Korea. sCr was not able to detect the early deterioration of renal function in NB patients. Co-morbid diabetes, small bladder volume, recurrent urinary tract infection, and proteinuria were significantly associated with CKD in the multivariable analysis. CONCLUSION: Chronic kidney disease prevalence was more than three times higher in NB patients than in the general population despite recent progress in the medical care of NB. Co-morbid diabetes, small bladder volume, recurrent urinary tract infection, and proteinuria seem to be the risk factors for CKD development in NB.

Cystatin C-calculated Glomerular Filtration Rate-A Marker of Early Renal Dysfunction in Patients With Neuropathic Bladder.

OBJECTIVE: To asses if cystatin c-calculated glomerular filtration rate (GFR) can reveal chronic kidney disease (CKD) not detected by creatinine-based calculations in a larger prospective cohort of children with myelomeningocele (MMC). Wheelchair-bound MMC patients frequently have low muscle mass, and assessing renal deterioration based on creatinine-based GFR is imprecise. MMC patients are also at risk for end-stage renal disease. METHODS: Prospectively enrolled patients with MMC underwent annual serum creatinine and cystatin c testing. Anthropometric measurements were obtained from clinic visit. The modified (bedside) Schwartz formula for creatinine-based GFR and the Zappitelli cystatin C formula were utilized for calculation. The exclusion criteria were patients with reduced GFR (CKD stage 2) or chronic CKD (CKD stage 3 and greater); these patients were excluded from analysis on the premise that they had already been identified for closer renal monitoring. RESULTS: A total of 131 patients were included in the analysis. The median creatinine-based estimated GFR was 126.5 mL/min/1.73 m2 (range: 22-310). The median cystatin C-based estimated rate was 98.5 mL/min/1.73 m2 (range: 16-171), yielding an absolute median rate reduction of 30.2%. Using cystatin c-calculated GFR, CKD stage was upgraded from stage 1 to ≥2 in 34 patients (26%). CONCLUSION: In MMC patients with poor muscle mass, cystatin C-based GFR is more sensitive than creatinine-based GFR in detecting early CKD. In this high-risk population, serial cystatin C estimation is a valuable tool in identifying children who may benefit from early nephrology referral and intervention.

Preoperative renal scar as a risk factor of postoperative metabolic acidosis following ileocystoplasty in patients with neurogenic bladder.

OBJECTIVES: We investigated relation of preoperative renal scar to incidence of postoperative metabolic acidosis following ileocystoplasty in patients with neurogenic bladder. PATIENTS: Thirty patients with neurogenic bladder, who underwent ileocystoplasty, were enrolled in the present study. Median age at ileocystoplasty was 13.9 years and median follow-up period after ileocystoplasty was 8.2 years. Metabolic acidosis was defined based on the outlined criteria: base excess (BE) is less than 0 mmol l(-1). Preoperative examination revealed that no apparent renal insufficiency was identified in blood analysis, although preoperative (99m)Tc-DMSA scintigraphy indicated abnormalities such as renal scar in 14 patients (47%). Incidence of postoperative metabolic acidosis was compared between patients with and without preoperative renal scar, which may reflect some extent of renal tubular damage. RESULTS: Postoperative metabolic acidosis was identified in 13 patients (43%). Incidence of postoperative metabolic acidosis was significantly higher in patients with renal scar (11/14, 79%) compared with patients without renal scar (2/16, 13%; P<0.01). Particularly, all eight patients who had bilateral renal scars showed metabolic acidosis postoperatively. Compared with patients without preoperative renal scar, pH (P<0.05) and BE (P<0.01) were significantly lower postoperatively in patients with preoperative renal scar. However, there was no significant difference in PCO2. Hyperchloremia was observed in each patient with or without preoperative renal scar. CONCLUSION: Incidence of postoperative metabolic acidosis was significantly implicated in preoperative renal scar. If renal abnormalities are preoperatively identified in imaging tests, we need to care patients carefully regarding metabolic acidosis and subsequent comorbidities following ileocystoplasty.

PSA levels in men with spinal cord injury and under intermittent catheterization.

AIM: To evaluate serum PSA levels of patients with spinal cord injury (SCI) submitted or not to CIC in comparison to those of the general population. METHODS: We retrospectively studied 140 men with SCI admitted in our department from January 2005 to May 2009. Thirty-four SCI patients had PSA levels available, comprising 21 under CIC and 13 without CIC. Patients under CIC performed it 4-6 times a day and mean time of catheterization was 72.4 months (range 30-192). The most common etiology of SCI was fall from height (33%), followed by car/motorcycle crashes (15%). Control group was composed by 670 healthy men that were referred to our service to evaluation of Kidney donation or cancer prostate screening. We used Student's t-test and variance analysis (ANOVA) for age and PSA comparison between the groups. RESULTS: Overall, patients with SCI and controls had similar mean age (54 vs. 57 years old, P = 0.11) and mean PSA level (1.81 vs. 1.95 ng/ml, P = 0.66). SCI patients were divided into with and without CIC. Patients without CIC had similar mean age (60 vs. 57 years old, P = 0.11) and similar PSA values when compared to controls (1.72 vs. 1.95 ng/ml, P = 0.89). Patients under CIC were compared to controls with similar age (50 vs. 47 years, P = 0.0332) and their PSA levels were greater (1.86 vs. 0.79 ng/ml, P = 0.026). CONCLUSION: Clean intermittent catheterization increased PSA levels approximately doubling its value.

[Estimation of GFR from serum creatinine and cystatin C-A comparison of 2 methods in patients with neurogenic bladder due to myelomeningocle (MMC)]. / Szacowanie GFR na podstawie wartosci kreatyniny i cystatyny C--porównanie dwóch metod w grupie pacjentów z pecherzem neurogennym w przebiegu przepukliny oponowo-rdzeniowej (MMC).

UNLABELLED: Glomerular filtration rate (eGFR) calculated from serum creatinine can be overestimated in patients with muscle mass deficits. AIM: The aim of this study was to compare eGFR calculated from serum levels of creatinine and cystatin C in a group of patients with neurogenic bladder due to MMC. MATERIAL AND METHODS: GFR calculations were performed for 67 patients using Schwartz formula for creatinine measured by colorimetric method and Filler formula for cystatin C measured by immunonephelometric method. RESULTS: Statistically significant lower eGFR values were obtained with calculations based on cystatin C levels. CONCLUSION: Cystatin C is a useful marker for GFR estimations in patients with reduced muscle mass.

Inflammatory C-reactive protein and cytokine levels in asymptomatic people with chronic spinal cord injury.

OBJECTIVE: To determine the relation between serologic markers of information and clinical characteristics of people with chronic spinal cord injury (SCI). DESIGN: Cross-sectional study. SETTING: Academic medical center SCI outpatient clinic. PARTICIPANTS: Convenience sample of 37 men with chronic SCI and 10 healthy control subjects. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). RESULTS: The following results achieved statistical significance at P less than .05. Asymptomatic chronic SCI patients differed from referent controls with respect to serum CRP levels but not IL-6 or TNF-alpha. In SCI patients, higher levels of CRP correlated negatively with hemoglobin and albumin levels. A longer time since injury correlated with lower TNF-alpha values, whereas higher TNF-alpha levels correlated with higher serum albumin. Pressure ulcers and indwelling urinary catheters were associated with higher mean levels of CRP but not of the cytokines TNF-alpha and IL-6. Intermittent urinary catheterization was associated with lower levels of CRP when compared with other methods of bladder management. CONCLUSIONS: Asymptomatic people with long-term SCI, especially those with indwelling urinary catheters, showed serologic evidence of a systemic inflammatory state. There was no evidence of an elevation in proinflammatory cytokines. Detection of an ongoing systemic inflammatory response in apparently healthy people with indwelling urinary catheters and small skin ulcers further supports the aggressive pursuit of catheter-free voiding options and pressure ulcer healing.

Urine 8-isoprostane F2alpha concentrations in patients with neurogenic bladder due to spinal cord injury.

BACKGROUND: Isoprostanes are prostaglandin-like end products of arachidonic acid peroxidation that are produced by a free radical-catalyzed mechanism. Considering its free radical-dependent formation and potent contractor effect, it is postulated that isoprostane 8-iso PGF2alpha may play an important role in oxidative stress-related smooth muscle dysfunction. These substances may also influence bladder activity directly by effects on the smooth muscle. The present study was designed to measure traditional biochemical parameters (MDA, TAS, vitamin E) in plasma and 8-iso PGF2alpha concentrations in urine of patients with spinal cord injury and to evaluate the relation of urinary isoprostane concentrations to the bladder function. METHODS: All spinal cord patients underwent urodynamic evaluations. The biochemical tests were performed in both hyperreflexic bladder group (n = 23) and areflexic bladder group (n = 10), and the findings were compared to those of the patients with normally functioning bladder (controls, n = 19). RESULTS: Urine 8-iso PGF2alpha concentrations were significantly increased in hyperreflexic group (median value 0.89 pg/mg creatinine) compared to both control (0.52 pg/mg creatinine) and areflexic groups (p < 0.001). The lowest concentrations of urinary 8-iso PGF2alpha were observed in the areflexic group (0.22 pg/mg creatinine), and these were positively correlated to the plasma MDA concentrations in areflexic patients (p = 0.05; r = 0.684). CONCLUSION: Isoprostanes may be involved in the pathogenesis of neurogenic bladder dysfunction. It may be of value to determine the urinary concentrations of 8-iso PGF2alpha in order to distinguish areflexic bladders from the hyperreflectics.

Hyperammonaemia due to Klebsiella infection in a neuropathic bladder.

A boy with a neuropathic bladder and a single hydronephrotic kidney developed hyperammonaemic encephalopathy during a urinary tract infection with Klebsiella oxytoca. Although particularly associated with Proteus infections and prune belly syndrome, hyperammonaemia can complicate infection with any urease-producing bacteria if there is urinary stasis.

Ciprofloxacin as prophylaxis for urinary tract infection: prospective, randomized, cross-over, placebo controlled study in patients with spinal cord lesion.

To evaluate the efficacy of low-dose long-term treatment with ciprofloxacin in the prevention of recurrent urinary tract infections in patients with spinal cord lesions and neurogenic bladder dysfunction, a prospective, randomized, cross-over, placebo-controlled study was performed. The study period was 12 months long, including 6 months of treatment with 100 mg. ciprofloxacin at night and 6 months of placebo treatment. The study was completed by 18 men and 3 women, median age 38 years (range 19 to 73 years). Within the last 12 months before inclusion into the study, the patients had between 3 and 14 urinary tract infections (mean 5.8) treated with antimicrobial agents. The number of urinary tract infections treated with antimicrobial agents during 6 months of ciprofloxacin prophylaxis was 5 and during the 6 months of placebo treatment it was 59 (p < 0.00005) [corrected]. Fecal specimens showed supercolonization with ciprofloxacin resistant bacteria (Acinetobacter calcoaceticus) in 1 instance. No severe side effects were observed. Ciprofloxacin at a dose of 100 mg. at night was efficacious in preventing urinary tract infections during 6 months in patients with spinal cord lesions and neurogenic bladder dysfunction. After the controlled study 10 of the 21 patients used ciprofloxacin as prophylaxis for up to 39 months with a marked reduction in the pre-study infection frequency. In 1 patient ciprofloxacin resistant Escherichia coli was subsequently found in the feces.

[Effectiveness and tolerance of cefixime in bacterial urinary tract infections in patients with myelomeningocele]. / Wirksamkeit und Verträglichkeit von Cefixim bei bakteriellen Infektionen der Harnwege bei Patienten mit Myelomeningozele.

28 myelomeningocele patients (aged 2-30 years) with clinical symptoms of acute UTI participated in this open uncontrolled clinical trial at the Orthopedic University Hospital of Heidelberg (Dir.: Prof. Dr. H. Cotta). 4 patients were treated with 200 mg cefixime tablets bid, 24 patients received 4 mg/kg body weight cefixime suspension bid, according to age and weight of the patients. The duration of treatment was 6-10 days. Clinical and microbiological examinations were carried out before therapy as well as 1 day and 5 to 9 days after the end of treatment. The data of 25 patients could be evaluated for bacteriological and clinical efficacy. 5-9 days after treatment in 22 patients (88%) complete recovery was stated. In 3 patients a reinfection occurred. In 24 patients (96%) the baseline pathogens were eliminated under cefixime therapy. 5-9 days after the end of treatment in 3 patients reinfection was observed. Clinical side effects could be detected in 1 patient (vomiting). These results indicate that the oral cephalosporin cefixime is efficient and well tolerated in complicated UTI of myelomeningocele patients.

Urethral supersensitivity and occult urethral neuropathy.

The phenomenon of postural increases in urethral tone in patients with neuropathic bladder dysfunction has been investigated and, using the technique of simulated alterations in posture, a humoral response of urethral smooth muscle has been demonstrated. Serial measurements of circulating catecholamines have shown that a close correlation exists between the contraction of urethral smooth muscle and the variations in circulating catecholamines brought about as part of cardiovascular homeostasis. Identical urethral responses have been recorded in a group of neurologically intact patients who have urethral outflow obstruction, and it is speculated that these patients may have an occult urethral neuropathy.