A Multicenter Prospective Randomized Controlled Trial Comparing Cxbladder Triage to Cystoscopy in Patients With Microhematuria: The Safe Testing of Risk for Asymptomatic Microhematuria Trial.

PURPOSE: AUA guidelines for patients with microhematuria (≥3 red blood cells [RBC]/high-power field [hpf]) include cystoscopy for most over age 40 due to risk of urothelial cancer (UC). Cxbladder Triage (CxbT) is a urinary genomic test with UC negative predictive value of 99%. In this prospective randomized controlled trial, we compared cystoscopy use in a standard of care (SOC) arm vs a marker-based approach. MATERIALS AND METHODS: All patients with hematuria provided urine for a CxbT. Those categorized as lower risk (LR), defined as 3 to 29 RBC/hpf and minimal smoking history (<10 pack-years) were randomized between the test group provided with the CxbT result vs the SOC control group. Negative CxbT patients were offered omission of cystoscopy with surveillance. "Not lower risk" (NLR) patients (>30 RBC/hpf or >10 pack-year smoking history) had a CxbT but otherwise SOC. Patient decision and outcomes were recorded. RESULTS: Of 390 eligible patients, 255 were NLR and 135 were LR randomized to CxbT informed decision or SOC. The median age was 62 years (range 18-94) and 54% were male. Overall, 63% of CxbT tests were negative. For NLR patients, 82% had cystoscopy. In the LR control group, cystoscopy was performed in 67% of SOC and 27% in the test group (relative risk 0.41 [95% CI 0.27-0.61]). Compared to cystoscopy, CxbT had 90% sensitivity, 56% specificity, and 99% negative predictive value for UC. CONCLUSIONS: In this prospective randomized controlled trial, use of CxbT in patients with LR hematuria resulted in 59% reduction of cystoscopy use. This clinical utility of CxbT can reduce the burden of unnecessary cystoscopies.

Urinalysis is predictive for absence of urinary tract infection in men with and without catheters.

OBJECTIVES: To determine accuracy of negative urinalysis (UA) for predicting negative urine culture and the absence of urinary tract infection (UTI), and optimal urine culture growth cutoff for UTI diagnosis in men with and without urinary catheters. SUBJECTS AND METHODS: UAs with urine cultures within 1 week from adult men were identified and evaluated. Predictive values for the absence of UTI (absence of ≥1 of the following criteria: documentation of UTI diagnosis, antibiotic prescription, uropathogen presence on culture) were calculated. RESULTS: In total, 22 883 UAs were included. Negative UA had a high predictive value for negative urine culture (0.95, 95% confidence interval [CI]: 0.94-0.95) and absence of UTI (0.99, CI: 0.99-0.995) in the overall cohort. Negative UA also had a high predictive value for negative urine culture (0.93, CI: 0.90-0.95) and absence of UTI (0.99, CI: 0.98-0.999) in those with indwelling urinary catheters. The traditional threshold of culture growth of 100 000 colony-forming units (CFU)/mL did not capture 22% of UTIs. CONCLUSION: UA exhibits high predictive value for negative urine culture and absence of UTI in men, supporting a protocol wherein culture is only performed in the context of abnormal UA. The traditional 100 000 CFU/mL cut-off may have not captured a subset of UTI in the male population, and warrants further investigation.

Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

INTRODUCTION/PURPOSE: Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. MATERIALS/METHODS: Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. RESULTS: Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. CONCLUSIONS: All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

Ureteral Stents Harbor Complex Biofilms With Rich Microbiome-Metabolite Interactions.

PURPOSE: We sought to determine microbe-metabolite composition and interactions within indwelling ureteral stent biofilms, determine their association with patient factors including infection, and reconstitute biofilm formation on relevant surface materials in vitro. MATERIALS AND METHODS: Upon ureteral stent removal from patients, proximal and distal ends were swabbed. Samples were analyzed by 16S next-generation sequencing and metabolomics. A continuous-flow stir-tank bioreactor was used to reconstitute and quantify in vitro biofilm formation from stent-isolated bacteria on stent-related materials including silicone, polytetrafluoroethylene, polyurethane, polycarbonate, and titanium. Diversity, relative abundance, and association with clinical factors were analyzed with ANOVA and Bonferroni t-tests or PERMANOVA. Biofilm deposition by microbial strain and device material type were analyzed using plate counts and scanning electron microscopy following bioreactor incubation. RESULTS: All 73 samples from 37 ureteral stents harbored microbiota. Specific genera were more abundant in samples from stents wherein there was antibiotic exposure during indwelling time (Escherichia/Shigella, Pseudomonas, Staphylococcus, Ureaplasma) and in those associated with infection (Escherichia/Shigella, Ureaplasma). The enriched interaction subnetwork in stent-associated infection included Ureaplasma and metabolite 9-methyl-7-bromoeudistomin. Strains identified as clinically relevant and central to interaction networks all reconstituted biofilm in vitro, with differential formation by strain (Enterococcus faecalis most) and material type (titanium least). CONCLUSIONS: Ureteral stent biofilms exhibit patterns unique to stent-associated infection and antibiotic exposure during indwelling time. Microbes isolated from stents reconstituted biofilm formation in vitro. This work provides a platform to test novel materials, evaluate new coatings for anti-biofilm properties, and explore commensal strain use for bacterial interference against pathogens.

The Natural History and Composition of Urinary Catheter Biofilms: Early Uropathogen Colonization with Intraluminal and Distal Predominance.

PURPOSE: We sought to determine the composition and initiation site of bacterial biofilm on indwelling urinary catheters and to track biofilm progression with time. MATERIALS AND METHODS: Indwelling urinary catheters were collected from 2 tertiary care centers following removal from patients. Indwelling time was noted and catheters were de-identified. Catheters were sectioned, stained for biofilms and analyzed by spectrophotometry and visualization. Biofilm colonization patterns were analyzed using descriptive statistical analysis and bacterial composition was determined using next generation sequencing. RESULTS: We collected and analyzed a total of 33 catheters from 26 males and 7 females with indwelling time ranging from 15 minutes to 43 days. Biofilm colonization was consistently high on the region of the balloon for all indwelling times. After week 1 the distal third of the catheter had higher biofilm colonization than the proximal third (week 2 p=0.034). At all indwelling times the intraluminal surface of the catheter had greater biofilm colonization than the outer surface. Next generation sequencing detected potential uropathogenic bacteria in all 10 analyzed samples. CONCLUSIONS: The catheter balloon, its distal aspect and its lumen were the predominant locations of biofilm comprising uropathogenic bacteria. Strategies to prevent or treat biofilm should be targeted to these areas.

Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy.

BACKGROUND: Polycythemia (erythrocytosis) is a known side effect of testosterone (T) replacement therapy (TRT) and appears to correlate with maximum T levels. There is also a well-established association between obstructive sleep apnea (OSA) and the development of polycythemia, which confers additional long-term cardiovascular morbidity. Synergy between TRT and OSA in the development of polycythemia remains poorly understood. AIM: The objective of this study was to retrospectively assess the relationship of OSA and secondary polycythemia in hypogonadal men receiving TRT. METHODS: We performed a retrospective chart review of all men treated by a single provider from 2015 to 2019 for the diagnosis of hypogonadism. Patients who developed a hematocrit of 52% or greater were classified as having polycythemia. OSA was identified via clinical documentation or use of nocturnal continuous positive airway pressure. Demographics, laboratory values, treatment details, and comorbidities were recorded. Data were reported as mean ± SD for parametric variables and median [interquartile range] for non-parametric values. OUTCOME: The primary outcome of this study was the association between OSA and polycythemia in hypogonadal men on TRT. RESULTS: 474 men were included in this study. 62/474 (13.1%) men met the criteria for the diagnosis of polycythemia with a median hematocrit of 53.6 [interquartile range 52.6, 55.5]. Univariate analysis demonstrated a strong positive association between polycythemia and the concomitant diagnosis of OSA in hypogonadal men (P = .002). Even after correcting for age, body mass index (BMI), and peak T levels in the multivariate analysis (P = .01), this relationship remained significant with an odds ratio of 2.09 [95% CI 1.17, 3.76]. 37 men on TRT with polycythemia and OSA were included in the final cohort with a mean age of 59.2 ± 11.4 years, mean BMI of 32.4 ± 6.0, and median time from TRT initiation to polycythemia diagnosis of 3 years. All patients diagnosed with OSA were prescribed continuous positive airway pressure with poor compliance noted in 52.8% of men. 37.8% were managed via phlebotomy and 59.5% were managed via dose de-escalation of TRT. In hypogonadal men on TRT with polycythemia, BMI was the only risk factor strongly associated with OSA (P = .013). CLINICAL TRANSLATION: In hypogonadal men (particularly those with elevated BMI) on TRT who develop secondary polycythemia, a diagnosis of OSA should be strongly considered. STRENGTHS & LIMITATIONS: This is a single provider retrospective study and further studies are needed to assess generalizability. CONCLUSIONS: In this retrospective single-center cohort, the development of polycythemia in hypogonadal men on TRT was associated with an increased prevalence of OSA. Lundy SD, Parekh NV, Shoskes DA. Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy. J Sex Med 2020;17:1297-1303.

Male CP/CPPS: where do we stand?

INTRODUCTION: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), commonly encountered in urologic practice, carries with it a stigma of poor understanding, ineffective treatment, and significant financial and quality of life burden. MATERIALS AND METHODS: This clinically practical review is based on the authors' personal clinical experience in interpretation and application of currently available evidence. RESULTS: Significant progress has been made in terms of classification and evaluation of the disease, leading to encouraging improvements in treatment outcomes. The Chronic Prostatitis Symptom Index (CPSI) is a helpful tool in clinical evaluation and has proven invaluable for research purposes, while UPOINT has demonstrated the heterogeneity of the disease and provides physicians with a uniquely patient-centered approach to treatment. The importance of the microbiome in the evaluation of CP/CPPS patients has yet to be fully appreciated. While personalized, multi-modal therapy appears to be the key to treatment, the addition of pelvic floor physiotherapy (PFPT) with injection of trigger points, and psychosocial therapies to the multi-modal approach armamentarium are promising advances. Innovative interventional approaches are encouraging but require study. CONCLUSIONS: While encouraging therapies have been added to personalized, multi-modal treatment strategies, newer innovative therapies appear promising for improved treatment of CP/CPPS patients.

Improving the utility of clinical phenotyping in interstitial cystitis/painful bladder syndrome: from UPOINT to INPUT.

INTRODUCTION: The phenotyping system UPOINT has proven effective in classifying patients with Urologic Pelvic Pain Syndromes in a clinically meaningful way and to guide therapy. While highly successful in men with chronic pelvic pain syndrome (CPPS), UPOINT is more limited in patients with interstitial cystitis/painful bladder syndrome (IC/PBS) since by definition all patients have the urinary and organ specific phenotype. Furthermore, AUA guidelines recommend a sequential tiered approach to therapy rather than the multimodal UPOINT scheme. We sought to modify UPOINT to be more practical and efficacious for IC/PBS. MATERIALS AND METHODS: We developed a new phenotype by removing the urinary and organ specific domains from UPOINT and adding a Hunner's ulcers (U) domain, since these patients benefit from phenotype specific therapies (fulguration, cyclosporine). This yields 'INPUT': infection, neurologic/systemic, psychosocial, ulcers and tenderness of muscles. We applied this system retrospectively to our previously validated upointmd.com IC/PBS database. Symptoms were measured by the Genitourinary Pain Index (GUPI) (valid for men and women). The database was searched for patients with complete data to assess the INPUT domains and include GUPI. Men were included if they reported pain relieved by voiding and/or presence of Hunner's ulcers. Groups were compared with ANOVA, Mann-Whitney, t test or chi squared when appropriate and correlated with Spearman r. RESULTS: There were 239 patients, 154 female (64%) with age range 18-79 (mean 41.8). Incidence of domains was infection 11%, neurologic/systemic 51%, psychosocial 81%, ulcers 18% and tenderness 85%. Mean total domains was 2.46 (range 0-5) and 65% had 2 or 3 positive domains while only 5% had none. There was a stepwise increase in GUPI score with increasing number of positive INPUT domains (ANOVA for differences between groups p < 0.0001. Correlation by Spearman r = 0.355 p < 0.0001). Presence of Hunner's ulcers increased mean symptom score (25.7 versus 29.7, p = 0.004) and indeed each of the domains significantly increased total GUPI score except for Infection. CONCLUSIONS: The INPUT phenotype in IC/PBS appears to replicate the validity and potential clinical utility of UPOINT in CPPS. Patients have a diversity of phenotypes and more positive domains correlate with more severe symptoms. Since 95% of patients have at least 1 positive domain it may benefit patients to receive multimodal therapy up front for these extra domains (eg. pelvic floor physical therapy, fulguration of ulcers) rather than relying on a sequential tiered approach.

Bacterial prostatitis.

PURPOSE OF REVIEW: The review provides the infectious disease community with a urologic perspective on bacterial prostatitis. Specifically, the article briefly reviews the categorization of prostatitis by type and provides a distillation of new findings published on bacterial prostatitis over the past year. It also highlights key points from the established literature. RECENT FINDINGS: Cross-sectional prostate imaging is becoming more common and may lead to more incidental diagnoses of acute bacterial prostatitis. As drug resistance remains problematic in this condition, the reemergence of older antibiotics such as fosfomycin, has proven beneficial. With regard to chronic bacterial prostatitis, no clear clinical risk factors emerged in a large epidemiological study. However, bacterial biofilm formation has been associated with more severe cases. Surgery has a limited role in bacterial prostatitis and should be reserved for draining of a prostatic abscess or the removal of infected prostatic stones. SUMMARY: Prostatitis remains a common and bothersome clinical condition. Antibiotic therapy remains the basis of treatment for both acute and chronic bacterial prostatitis. Further research into improving prostatitis treatment is indicated.

Analysis of Gut Microbiome Reveals Significant Differences between Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome is a common disorder with heterogeneous etiologies and clinical features. The gut microbiome is a metabolically active ecosystem linked to systemic conditions (gut-brain axis). We hypothesize that the gut microbiome will show alterations between patients with chronic pelvic pain syndrome and controls. MATERIALS AND METHODS: We identified patients with chronic pelvic pain syndrome and controls who were asymptomatic or only had urinary tract symptoms. After rectal examination the soiled glove tip was immersed in sterile saline and stored on ice. Symptom severity was measured with the NIH-Chronic Prostatitis Symptom Index and clinical phenotype with UPOINT. Total DNA was extracted from the pellet of samples. MiSeq sequencing of bacterial specific 16S rRNA capture was performed. Taxonomic and bioinformatic analyses were performed using principal coordinate analysis, QIIME and LEfSe algorithms. RESULTS: There were 25 patients and 25 controls with complete data. Mean age was similar (chronic pelvic pain syndrome 52.3 vs control 57.0 years, p=0.27). For patients with chronic pelvic pain syndrome median symptom duration was 48 months, mean Chronic Prostatitis Symptom Index was 26.0 and mean UPOINT domain was 3.6. Three-dimensional UniFrac principal coordinate analysis revealed tighter clustering of controls in a space distinct from the wider clustering of cases (p=0.001) with cases having decreased alpha diversity (p=0.001). Compared to controls, 3 taxa were overrepresented in cases and 12 were underrepresented, eg Prevotella. CONCLUSIONS: Patients with chronic pelvic pain syndrome have significantly less gut microbiome diversity which clusters differently from controls, and robustly lower counts of Prevotella, with separation sufficient to serve as a potential biomarker. The gut microbiome may serve as disease biomarker and potential therapeutic target in chronic pelvic pain syndrome.

'Spousal Revenge Syndrome'--description of a new chronic pelvic pain syndrome patient cohort.

Psychological factors may play a role in the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This case series describes a cohort of 10 men presenting with CP/CPPS whose symptoms began after an extramarital sexual encounter, who strongly believed they had a sexually transmitted infection (STI) despite negative testing, and who have had no improvement with empiric antibiotic treatment. Patients' clinical presentation and physical exam findings are reviewed. All men were clinically phenotyped with the UPOINT system. Pelvic floor spasm and not infection was prominent in these men. Treatment recommendations are proposed and compliance assessed.

Patients with Pelvic Floor Muscle Spasm Have a Superior Response to Pelvic Floor Physical Therapy at Specialized Centers.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome is a common condition that often requires multimodal therapy. Patients with chronic pelvic pain syndrome have a high incidence of pelvic floor spasm, which can be treated with pelvic floor physical therapy. However, this is a specialized skill. We compared outcomes of pelvic floor physical therapy as part of multimodal therapy in patients with chronic pelvic pain syndrome between those treated at our institution and elsewhere. MATERIALS AND METHODS: We identified patients from our chronic pelvic pain syndrome registry with pelvic floor spasm who were seen between 2010 and 2014 for more than 1 visit. Patient phenotype was assessed with the UPOINT system and symptom severity was determined by the National Institutes of Health CPSI. A 6-point decrease in CPSI was used to define patient improvement. RESULTS: A total of 82 patients fit the study criteria. Mean age was 41.6 years (range 19 to 75) and median symptom duration was 24 months (range 3 to 240). Mean CPSI was 26.8 (range 10 to 41), the median number of positive UPOINT domains was 3 (range 1 to 6) and 27 patients (32.9%) were treated locally. At followup 9 patients had refused pelvic floor physical therapy, and 24 and 48 had undergone pelvic floor physical therapy elsewhere and at CCF, respectively. The mean change in CPSI was 1.11 ± 4.1 in patients who refused, -3.46 ± 6.7 in those treated elsewhere and -11.3 ± 7.0 in those treated at CCF (p <0.0001). Individual improvement was seen in 1 patient (11%) who refused, 10 (42%) treated elsewhere and 38 (79.2%) treated at CCF (p <0.0001). On multivariable analysis only physical therapy at CCF (OR 4.23, p = 0.002) and symptom duration (OR 0.52, p = 0.03) predicted improvement. CONCLUSIONS: Pelvic floor physical therapy can be effective for chronic pelvic pain syndrome in patients with pelvic floor spasm. However, the outcome depends on specialty training and experience of therapists.

Phenotype, symptom severity and treatment in a 'cured' cohort of chronic pelvic pain syndrome patients.

INTRODUCTION: To identify a cohort of chronic pelvic pain syndrome (CPPS) patients who considered their symptoms completely resolved and analyze their demographics, clinical phenotype, treatments and NIH-Chronic Prostatitis Symptom Index (CPSI) scores. MATERIALS AND METHODS: We identified 35 CPPS patients who at the follow up, reported their symptoms completely resolved ('cured'). Demographics, UPOINT phenotypes, treatments, and CPSI scores were examined. We also compared these variables to a database of 220 previously evaluated CPPS patients. RESULTS: Patients ranged in age from 19 to 72 years. Median follow up was 12 months. Mean change in CPSI sub scores before and after therapy were pain 9.7 ± 3.8 to 2.7 ± 2.9, urinary 4.0 ± 2.8 to 1.1 ± 1.2, QoL 8.1 ± 2.7 to 2.3 ± 2.5, and total 21.8 ± 6.6 to 6.2 ± 1.0 (all p < 0.0001). Only 9 (26%) patients reported a total score of 0. Comparing this 'cured' group to a previously published cohort of phenotyped CPPS patients, the 'cured' group had lower starting total and pain CPSI scores (21.8 versus 25.0 p = 0.007; 9.7 versus 11.5 p = 0.006 respectively). CONCLUSIONS: Many men with CPPS can reach a subjective cure, however, the majority do not reach a CPSI score of 0. This group of "cured" patients is similar to our typical tertiary referral cohort in terms of age and phenotype but differs in having slightly lower pre-treatment CPSI scores.

Outcomes of Prostate Biopsy in Men with Hypogonadism Prior or During Testosterone Replacement Therapy.

INTRODUCTION: The relationship between Testosterone Replacement Therapy (TRT) and prostate cancer remains controversial. Most TRT studies show no change in prostate specific antigen (PSA) but some men do have PSA rise or develop an abnormal digital rectal exam (aDRE). Our objective was to examine the biopsy results of men with symptomatic hypogonadism before or during therapy. MATERIALS AND METHODS: Data was extracted from our medical record on men with hypogonadism who had a prostate biopsy within the past 4 years done by 3 Urologists with guideline driven practice patterns. RESULTS: 96 men were identified. Mean age at biopsy was 63 (range 40-85) and median PSA was 3.78ng/dL (0.5-662). Of the 61 men not on TRT, median PSA was 4.34 (0.5 to 662) and mean total testosterone 254 (191-341). There were 29 (47.5%) prostate cancers found (6 Gleason score 6, 13 Gleason score 7, 10 Gleason score 8 or 9). Of the 35 men on TRT, median PSA was 3.27 (0.5 to 13.7). The %PSA increase ranged from 2 to 251% (mean 93.5%). Mean total testosterone was 383 (146-792). Of the 14 men treated < 2 years, none had cancer. Of the 21 men treated 2 or more years 5 had cancer (2 Gleason score 6, 3 Gleason score 7). CONCLUSIONS: Men with hypogonadism and a clinical indication for biopsy often have prostate cancer, many high grade. No men with an initial PSA rise on TRT had cancer. Men on long term TRT should be monitored with PSA and DRE per guidelines.

Low testosterone at time of transplantation is independently associated with poor patient and graft survival in male renal transplant recipients.

PURPOSE: Low testosterone is common in men with renal disease and it increases the risk of death in those on dialysis. We studied serum testosterone at transplantation and correlated it with patient and graft outcomes. MATERIALS AND METHODS: We identified serum samples collected and frozen at the time of transplantation in male recipients of primary kidney transplants done more than 6 years ago at our institution. In 197 recipients there was sufficient serum to determine total testosterone. We analyzed contingency outcomes by the Fisher exact test, continuous values by the Student t-test and survival by the Gehan-Breslow-Wilcoxon test. RESULTS: Mean patient age was 48.9 years (range 14 to 75). There were 100 living and 97 cadaveric donors, and 53 recipients (27%) had diabetes. Mean ± SD serum testosterone was 477 ± 251.3 ng/dl (range 48 to 2,013). Testosterone was low (less than 220 ng/dl) in 24 patients. Age did not correlate with testosterone. Low testosterone recipients had worse 1-year patient survival (75% vs 95%, p = 0.003), 3-year patient survival (62.5% vs 86.1%, p = 0.008), 1-year graft survival (62.5% vs 92.4%) and 3-year graft survival (50% vs 76.3%, p = 0.01). Survival curves showed significantly worse patient survival (p = 0.004) and graft survival (p = 0.02) for low testosterone. On multivariable analysis low testosterone was independently associated with patient death (HR 2.27, 95% CI 1.19-4.32) and graft loss (HR 2.05, 95% CI 1.16-3.62). CONCLUSIONS: Low testosterone at transplantation is associated with patient death and graft loss. If due to causality, testosterone therapy may impact survival. Without causality low testosterone may still be a marker for posttransplant risk.

Serum testosterone levels and mortality in men with CKD stages 3-4.

BACKGROUND: Hypogonadism in men (total testosterone <350 ng/dL) is associated with higher risk of cardiovascular disease and mortality in men on dialysis therapy. We evaluated the association of hypogonadism with all-cause mortality in men with non-dialysis-dependent chronic kidney disease (CKD). STUDY DESIGN: Retrospective, cohort study. SETTING & PARTICIPANTS: 2,419 men with CKD stages 3-4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2) who had total testosterone measured for cause between January 1, 2005, and October 31, 2011, at a tertiary-care center in Cleveland, OH. PREDICTORS: Total testosterone measured using an immunoassay measurement in 3 forms: (1) categorized as low or testosterone replacement therapy versus normal, (2) continuous log testosterone, and (3) quintiles (100-226, 227-305, 306-392, 393-511, and 512-3,153 ng/dL). OUTCOMES: Factors associated with low total testosterone level and the association between low total testosterone level and all-cause mortality were evaluated using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves. RESULTS: Hypogonadism was found in 1,288 of 2,419 (53%) men. In a multivariable logistic regression analysis, African American ethnicity and higher estimated glomerular filtration rate were associated with lower odds of having hypogonadism. Diabetes and higher body mass index were associated with higher odds of having hypogonadism. 357 of 2,419 (15%) patients died during a median follow-up of 2.3 years. In the multivariate Cox model, testosterone level <350 ng/dL or testosterone replacement therapy was not associated with mortality. In a multivariable model also adjusted for testosterone supplementation, higher log testosterone was associated with significantly lower mortality (HR per 1 log unit, 0.70; 95% CI, 0.55-0.89). When compared to the highest quintile, the second lowest quintile of testosterone was associated with higher mortality (HR, 1.53; 95% CI, 1.09-2.16). LIMITATIONS: Single-center study, timing of testosterone testing, lack of adjustment for proteinuria, and sampling bias. CONCLUSIONS: Low total testosterone level may be associated with higher mortality in men with CKD stages 3-4, but more studies are needed.