Higher cardiovascular mortality in men with persistent dipstick hematuria.

BACKGROUND: We previously reported that dipstick hematuria (UH) was associated with higher all-cause mortality in men, but not in women. We extended the observation and examined the causes of death using repeated urinalysis in men. METHODS: Subjects were those who participated the Tokutei-Kenshin between 2008 to 2015 in seven districts. Using National database of death certificate, we identified those who might have died and confirmed further with the collaborations of the regional National Health Insurance agency and public health nurses. Dipstick results of 1 + and higher were defined as hematuria. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using the Cox proportional hazard analysis. We adjusted for age, body mass index, eGFR, proteinuria, comorbid condition (diabetes mellitus, hypertension, and dyslipidemia), past history (stroke, heart disease, and kidney disease), and lifestyle (smoking, drinking, walking, and exercise). RESULTS: A total of 170,119 men were studied and 70,350 (41.4% of the total) were re-examined next year. The prevalence of UH (-/-), UH (-/+), UH (±), and UH (+ /+) was 77.2% (N = 54,298), 14.0% (N = 9,838), 1.4% (N = 1014) and 7.4% (N = 5,200), respectively. We identified 1,162 deaths (1.7% of the total of the re-examined). The adjusted HR (95% CI) was 1.49 (1.22-1.81) for all-cause mortality and 1.83 (1.23-2.71) for cardiovascular death compared to those with UH (-/-), respectively. However, that for cancer mortality risk was not significant: 1.23 (0.92-1.64). CONCLUSIONS: In men, persistent dipstick hematuria is a significantly risk factor of all-cause mortality, in particular cardiovascular death among general screening participants.

Renal artery embolisation: indications and utilisation at Tygerberg Hospital.

BACKGROUND: To evaluate the indications, efficacy and outcomes of endovascular renal artery embolisation (RAE) in the management of renal haemorrhage, specifically in cases of non-iatrogenic origin. METHOD: This is a retrospective case note review of 92 patients who underwent RAE in the period from August 1999 to August 2014 at Tygerberg Hospital. RESULTS: Renal artery embolisation was performed in a total of 92 patients. The indication was traumatic renal injury in 60 patients (65.2%), with mean age 28.2 years. The mechanism of injury was stabbing (55.4%), blunt trauma (7.6%) and gunshot (2.2%). Digital subtraction angiography (DSA) showed pseudo-aneurysm in 32.6%, arteriovenous fistula in 19.6% and segmental artery injury in 13%. Embolisation success: 85% after one, 88.9% after a second attempt, with an overall success rate of 98.3% after two attempts. In 20 of the 92 patients (mean age 50.2 years) the indication was malignancy (21.7%). Other cases included iatrogenic haematuria (4.3%) and angiomyolipoma (3.3%). Embolisation was repeated in 16.3%, with eventual success rate of 93.8%. Post-embolisation syndrome was the most common complication, seen in 9.8% of all cases. Of the 9 patients who returned for follow-up with renogram imaging, 4 had a differential function of > 20% of the embolised kidney. CONCLUSION: Renal artery embolisation remains a very successful method of managing renal haemorrhage at this hospital, whether this results from trauma, malignancy, iatrogenic or other causes.

Hematuria Alone or in Combination with Proteinuria Is a Harbinger of Poor Prognosis in Patients with Non-Hodgkin Lymphoma.

BACKGROUND: Screening for hematuria is essential during health checkups in the general population. However, urine examinations in patients with cancer tend to be overlooked. This study attempted to demonstrate the novel utility of urinalysis in the assessment of the prognosis of non-Hodgkin lymphoma (NHL). METHODS: A longitudinal, retrospective cohort study was conducted to examine the association between hematuria and mortality in 294 patients with NHL. Urinalysis was performed using a dipstick test. A multivariate, logistic regression model was constructed to evaluate factors associated with the presence of hematuria. Statistical association between hematuria and the time to all-cause mortality was analyzed using Kaplan-Meier analysis, followed by multivariate proportional hazards regression analysis adjusted for covariates that might be related to mortality. RESULTS: The prevalence of hematuria alone and in combination with proteinuria was 11.6 and 5.1%, respectively. C-reactive protein was a significant factor associated with the presence of hematuria (OR [95% CI] 1.17 [1.03-1.34], p = 0.0194). The cumulative mortality was significantly higher in patients with hematuria alone (51.1%), proteinuria alone (47.1%), and both (66.7%), than in those with neither (24.3%). Moreover, the presence of hematuria alone was significantly associated with all-cause mortality (hazard ratio [95% CI] 1.78 [1.10-3.50], p = 0.0455), and patients with concomitant proteinuria were at the highest risk (4.01 [1.71-8.33], p = 0.0001). CONCLUSIONS: In patients with hematuric NHL, systemic inflammation is likely to develop to such a great extent that kidney damage occurs. Therefore, the presence of hematuria, alone or especially in combination with proteinuria, predicts a poor prognosis of NHL.

Hematuria as a risk factor for progression of chronic kidney disease and death: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: Hematuria is associated with chronic kidney disease (CKD), but has rarely been examined as a risk factor for CKD progression. We explored whether individuals with hematuria had worse outcomes compared to those without hematuria in the CRIC Study. METHODS: Participants were a racially and ethnically diverse group of adults (21 to 74 years), with moderate CKD. Presence of hematuria (positive dipstick) from a single urine sample was the primary predictor. Outcomes included a 50% or greater reduction in eGFR from baseline, ESRD, and death, over a median follow-up of 7.3 years, analyzed using Cox Proportional Hazards models. Net reclassification indices (NRI) and C statistics were calculated to evaluate their predictive performance. RESULTS: Hematuria was observed in 1145 (29%) of a total of 3272 participants at baseline. Individuals with hematuria were more likely to be Hispanic (22% vs. 9.5%, respectively), have diabetes (56% vs. 48%), lower mean eGFR (40.2 vs. 45.3 ml/min/1.73 m2), and higher levels of urinary albumin > 1.0 g/day (36% vs. 10%). In multivariable-adjusted analysis, individuals with hematuria had a greater risk for all outcomes during the first 2 years of follow-up: Halving of eGFR or ESRD (HR Year 1: 1.68, Year 2: 1.36), ESRD (Year 1: 1.71, Year 2: 1.39) and death (Year 1:1.92, Year 2: 1.77), and these associations were attenuated, thereafter. Based on NRIs and C-statistics, no clear improvement in the ability to improve prediction of study outcomes was observed when hematuria was included in multivariable models. CONCLUSION: In a large adult cohort with CKD, hematuria was associated with a significantly higher risk of CKD progression and death in the first 2 years of follow-up but did not improve risk prediction.

Association of dipstick hematuria with all-cause mortality in the general population: results from the specific health check and guidance program in Japan.

Background: Dipstick urine tests are used for general health screening in Japan. The effects of this screening on mortality have not been examined, especially with regard to hematuria. Methods: Subjects were those who participated in the 2008 Tokutei-Kenshin (nationwide specific health check and guidance program) in six districts in Japan. Using the national database of death certificates from 2008 to 2012, we identified subjects who might have died. We verified the candidates in collaboration with the regional National Health Insurance agency and public health nurses. Data were released to the research team supported by the Ministry of Health, Labor, and Welfare of Japan. Dipstick results of 1+ and higher were defined as hematuria (+). Hazard ratio (HR) [95% confidence interval (CI)] was calculated using the Cox proportional hazard analysis. Results: Among 112 115 subjects, we identified that 1290 had died by the end of 2012. In hematuria (-) subjects, the crude mortality rates were 1.2% (1.8% in men, 0.7% in women), whereas in hematuria (+) subjects, they were 1.1% (2.9% in men, 0.7% in women). After adjusting for age, body mass index, estimated glomerular filtration rate, proteinuria, comorbid condition (diabetes mellitus, hypertension and dyslipidemia), past history (stroke, heart disease and kidney disease) and lifestyle (smoking, drinking, walking and exercise), the HR (95% CI) for dipstick hematuria (+) in men was 1.464 (1.147-1.846; P = 0.003), whereas that for hematuria (-) was 0.820 (0.617-1.073; P = 0.151). Conclusions: Dipstick hematuria is significantly associated with mortality in men among Japanese community-based screening participants.

Macroscopic Hematuria After Conventional or Hypofractionated Radiation Therapy: Results From a Prospective Phase 3 Study.

PURPOSE: To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately hypofractionated radiation therapy (MHRT) for localized prostate cancer. METHODS AND MATERIALS: Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 months (range 6-143). RESULTS: Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval [CI] 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P=.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P=.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer-related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P=.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates. CONCLUSIONS: MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.

Long-term outcomes in a high-risk bladder cancer screening cohort.

OBJECTIVE: To evaluate the long-term outcomes in patients at high risk of bladder cancer who participated in a bladder cancer screening trial. MATERIALS AND METHODS: Patients who were classified as high risk based on age ≥50 years, ≥10 pack-years (combination of packs of tobacco per day and years of smoking) smoking and/or ≥15 years environmental exposure were enrolled in a one-time screening trial using a nuclear matrix protein 22 (NMP22) assay, between March 2006 and November 2007, at Dallas Veterans Affairs Hospital. We assessed the subsequent detection of smoking-related malignancies (bladder, lung and renal cell carcinoma [RCC]) in these patients up until 31 January 2014. Multivariable regression analysis was used to determine factors associated with bladder cancer diagnosis and survival. RESULTS: The study cohort included 925 patients, of whom 886 (95.8%) were smokers and 613 (66.3%) had received hazardous occupational exposure. At initial screening, 57 patients had a positive NMP22 test and two had bladder cancer. Another nine patients (1.0%) were diagnosed with bladder cancer during the median follow-up of 78.4 months. The bladder cancers were non-invasive (Ta) and seven were low grade and four high grade. RCC and lung cancer were diagnosed in 10 (1.1%) and 18 patients (1.9%), respectively. A total of 134 patients died, including three from RCC and 12 from lung cancer, but none from bladder cancer. Factors associated with worse overall survival on multivariable analysis were: lung cancer (hazard ratio [HR] 5.06; P < 0.001), microscopic or gross haematuria (HR 1.66; P = 0.006 and HR 2.11; P = 0.02, respectively), and >60 pack-years smoking history (HR 4.51; P = 0.037). CONCLUSION: At 6.5 years of follow-up, no patients in this high-risk cohort developed muscle-invasive bladder cancer. Lung cancer, haematuria and >60 pack-years smoking history are independent predictors of mortality. Other-cause mortality is an important consideration in patients undergoing bladder cancer screening.

Hemorrhagic Cystitis Requiring Bladder Irrigation is Associated with Poor Mortality in Hospitalized Stem Cell Transplant Patients

Purpose: To evaluate the overall prognosis of post-stem cell transplant inpatients who required continuous bladder irrigation (CBI) for hematuria. Materials and Methods: We performed a retrospective analysis of adult stem cell transplant recipients who received CBI for de novo hemorrhagic cystitis as inpatients on the bone marrow transplant service at Washington University from 2011-2013. Patients who had a history of genitourinary malignancy and/or recent surgical urologic intervention were excluded. Multiple variables were examined for association with death. Results: Thirty-three patients met our inclusion criteria, with a mean age of 48 years (23-65). Common malignancies included acute myelogenous leukemia (17/33, 57%), acute lymphocytic leukemia (3/33, 10%), and peripheral T cell lymphoma (3/33, 10%). Median time from stem cell transplant to need for CBI was 2.5 months (0 days-6.6 years). All patients had previously undergone chemotherapy (33/33, 100%) and 14 had undergone prior radiation therapy (14/33, 42%). Twenty-eight patients had an infectious disease (28/33, 85%), most commonly BK viremia (19/33, 58%), cytomegalovirus viremia (17/33, 51%), and bacterial urinary tract infection (8/33, 24%). Twenty-two patients expired during the same admission as CBI treatment (22/33 or 67% of total patients, 22/28 or 79% of deaths), with a 30-day mortality of 52% and a 90-day mortality of 73% from the start of CBI. Conclusions: Hemorrhagic cystitis requiring CBI is a symptom of severe systemic disease in stem cell transplant patients. The need for CBI administration may be a marker for mortality risk from a variety of systemic insults, rather than directly attributable to the hematuria.

Hemorrhagic Cystitis Requiring Bladder Irrigation is Associated with Poor Mortality in Hospitalized Stem Cell Transplant Patients.

PURPOSE: To evaluate the overall prognosis of post-stem cell transplant inpatients who required continuous bladder irrigation (CBI) for hematuria. MATERIALS AND METHODS: We performed a retrospective analysis of adult stem cell transplant recipients who received CBI for de novo hemorrhagic cystitis as inpatients on the bone marrow transplant service at Washington University from 2011-2013. Patients who had a history of genitourinary malignancy and/or recent surgical urologic intervention were excluded. Multiple variables were examined for association with death. RESULTS: Thirty-three patients met our inclusion criteria, with a mean age of 48 years (23-65). Common malignancies included acute myelogenous leukemia (17/33, 57%), acute lymphocytic leukemia (3/33, 10%), and peripheral T cell lymphoma (3/33, 10%). Median time from stem cell transplant to need for CBI was 2.5 months (0 days-6.6 years). All patients had previously undergone chemotherapy (33/33, 100%) and 14 had undergone prior radiation therapy (14/33, 42%). Twenty-eight patients had an infectious disease (28/33, 85%), most commonly BK viremia (19/33, 58%), cytomegalovirus viremia (17/33, 51%), and bacterial urinary tract infection (8/33, 24%). Twenty-two patients expired during the same admission as CBI treatment (22/33 or 67% of total patients, 22/28 or 79% of deaths), with a 30-day mortality of 52% and a 90-day mortality of 73% from the start of CBI. CONCLUSIONS: Hemorrhagic cystitis requiring CBI is a symptom of severe systemic disease in stem cell transplant patients. The need for CBI administration may be a marker for mortality risk from a variety of systemic insults, rather than directly attributable to the hematuria.

Haematuria: from identification to treatment.

Haematuria has a prevalence of 0.1% to 2.6%. Potential diagnoses may include infection, kidney stones, trauma, exercise or spurious causes, such as foods, drugs or menstruation, and a tumour. Approximately 20% of patients with haematuria have a urological tumour, with a further 20% found to have a significant underlying pathology. Haematuria is subsequently known as the 'classic presentation' of bladder cancer with 70-80% of patients experiencing painless, gross (visible) haematuria. However, in all cases of visible haematuria, a tumour should be suspected until proven otherwise. A patient with visible haematuria requires urgent, stringent investigation, warranting specialist assessment and subsequent selective referral through a series of patient-centred investigations at a haematuria clinic. One-stop clinics have been shown to improve the patient experience in early diagnosis of potentially life-threatening conditions. Yet despite morbidity and mortality from bladder cancer increasing, the haematuria service has remained largely unchanged for several decades. This paper will discuss the tests and investigations that need to be undertaken in an individual with either visible or non-visible haematuria, and outline the care that is needed to support patients through the investigation process, with special focus on bladder tumour.

Clinical significance of microscopic haematuria in diabetic nephropathy in type 2 diabetes patients with overt proteinuria.

AIM: Although some patients with diabetic nephropathy with overt proteinuria have microscopic haematuria, the pathological characteristics and clinical significance related to microscopic haematuria have not yet been clarified. The aim of the present study was to clarify the pathological characteristics and clinical significance of microscopic haematuria. METHODS: Eighty-four type 2 diabetes patients with overt proteinuria and biopsy-confirmed diabetic nephropathy were enrolled. The clinical and histological findings were compated between the patients with persistent haematuria (group 1, n=25) and those with persistent non-haematuria (group 2, n=23) after renal biopsy. The association between persistent haematuria and renal outcome at 5 years was examined. Histological scoring was made according to the original system and that of Tervaert et al. RESULTS: Thirty-six patients (43%) had microscopic haematuria at the time of renal biopsy. Age was significantly smaller and blood pressure was significantly greater in group 1 than in group 2 (age: group 1, 56 ± 10 years; group 2, 62 ± 9 years; P=0.03, systolic blood pressure: group 1, 152 ± 16 mm Hg; group 2, 140 ± 16 mm Hg; P=0.01). There were no significant differences in histological parameters between the two groups. A logistic regression model demonstrated that arteriolar hyalinosis was significantly associated with persistent haematuria (OR=2.81; P=0.04). There were no significant differences in changes in reciprocal serum creatinine and rates of doubling of serum creatinine after renal biopsy between the two groups. CONCLUSION: Although arteriolar hyalinosis was associated with persistent haematuria, the clinical significance of microscopic haematuria was minor in diabetic nephropathy in type 2 diabetes patients with overt proteinuria.

Clinical prognostic factors and survival outcome in renal cell carcinoma patients--a malaysian single centre perspective.

BACKGROUND: This study concerns clinical characteristics and survival of renal cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well as the prognostic significance of presenting symptoms. MATERIALS AND METHODS: The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis. RESULTS: The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, 9.5±4.3cm, was larger than non palpable masses, 5.3±2.7cm (p<0.001). CONCLUSIONS: This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.

Incidence and features of dual anti-GBM-positive and ANCA-positive patients.

AIMS: Goodpasture's syndrome, glomerulonephritis and pulmonary haemorrhage, may be due to a variety of causes. Rarely, patients with Goodpasture's syndrome present with both anti-glomerular basement membrane (GBM) and antineutrophil cytoplasmic antibody (ANCA). The aim of this report was to determine the incidence, clinical features, management and outcomes of patients presenting with concurrent ANCA and anti-GBM disease in Auckland. METHODS: Potential patients were identified by an electronic search of serology for ANCA and anti-GBM antibody, diagnostic renal biopsy, or in-hospital admissions using ICD9 and ICD10 codes between 1998 and 2008. A retrospective case-note review of all potential cases was performed. RESULTS: Six cases were identified: two women and four men. The incidence was estimated at 0.47 cases per million people per year. The mean age of presentation was 59 years (range 25-85 years). One patient was a smoker and two patients were ex-smokers. All subjects were anaemic, had haemoptysis and an abnormal chest X-ray at presentation. The mean creatinine at presentation was 225 µmol/L (range 126-406 µmol/L); all patients had haematuria and proteinuria. All patients received corticosteroids and cyclophosphamide. Two patients were not plasma exchanged and died. Four patients received plasma exchange and are alive. One patient had a clinical relapse 6 years after their initial presentation and is on renal replacement therapy. CONCLUSION: Concurrent ANCA and anti-GBM disease is rare. The mortality rate is high. Aggressive immunosuppression with steroids, cyclophosphamide and plasma exchange can induce remission and preserve renal function. Long-term monitoring for relapses should occur.

Hematuria due to adenoviral infection in bone marrow transplant recipients.

Late-onset hemorrhagic cystitis (HC) caused by adenovirus (AdV) infection is a common complication in hematopoietic stem cell transplantation (HSCT) recipients. However, limited information exists regarding adenovirus-associated HC. We report a retrospective study of 84 hematopoietic stem cell transplant recipients that evaluated the incidence and risk factors for AdV-induced HC. The development of HC was strongly related to adenoviral infection (P = .004). Among 13 patients who developed late-onset HC, AdVs were identified as a causative agent in 10 cases. AdV preferentially affected younger (P = .013) and male patients. Affected subjects had been transplanted for either malignant (7/10) or nonmalignant disorders (3/10). Most cases of AdV-hematuria were self-limited single or recurrent mild hemorrhagic episodes (P = .000), occurring at a median of 41 days after transplantation and lasting an average of 4 days. Viral load in patients with AdV-induced HC was similar to infected subjects who did not develop HC (2.5 × 10(3) vs 3.4 × 10(3) copies/mL). We HC occurring before 200 days was associated with a greater risk of a fatal outcome (P = .002) but occurrence of AdV infection did not affect a patient's survival. Our study confirmed the suggestion that non-AdV coinfections may worsen the course of AdV-HC.

Efficacy and survival associated with cystoscopy and clot evacuation for radiation or cyclophosphamide induced hemorrhagic cystitis.

PURPOSE: We assessed the outcome of patients with hemorrhagic cystitis severe enough to require cystoscopy and clot evacuation. MATERIALS AND METHODS: We retrospectively evaluated the records of 33 patients with cyclophosphamide or radiation induced hemorrhagic cystitis treated with cystoscopy. RESULTS: Mean followup of living patients was 76 months. Of 33 patients 20 (61%) had resolution of hematuria after single cystoscopy unrelated to hemorrhagic cystitis etiology. Only 4 of 11 patients (36%) had resolution after 2 or more cystoscopies, and all were in the radiation induced hemorrhagic cystitis group (4 of 6, 67%) with none in the cyclophosphamide induced hemorrhagic cystitis group (0 of 5, p = 0.02). Hematuria was refractory to cystoscopy in 9 patients and ileal conduits were created in 4. Kaplan-Meier overall survival at 1, 2 and 5 years was 58%, 51% and 43%, respectively, with survival tending to be worse in patients who received cyclophosphamide for bone marrow transplantation induction. Of the 18 deaths 3 were due to complications of hemorrhagic cystitis, 13 were due to the disease underlying the hemorrhagic cystitis and 2 were unrelated. CONCLUSIONS: The response of hemorrhagic cystitis to single cystoscopy and clot evacuation is reasonable but response to subsequent cystoscopy (unless the hemorrhagic cystitis is radiation induced) is less likely, so alternate interventions should be considered if hematuria does not resolve after initial cystoscopy. Patients with hemorrhagic cystitis requiring cystoscopy have a poor prognosis even if hematuria resolves, although most deaths are related to the disease underlying the hemorrhagic cystitis rather than its direct result.

Dense deposit disease: clinicopathologic study of 32 pediatric and adult patients.

BACKGROUND AND OBJECTIVES: Dense deposit disease (DDD) is a rare disorder that most commonly affects children. This study reports the largest North American series addressing clinicopathologic and outcome differences in children and adults. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Thirty-two patients with DDD were analyzed from the archives of Columbia University between 1977 and 2007. Characteristic intramembranous electron-dense deposits defined all diagnoses. RESULTS: The cohort included 14 children (<16 yr) and 18 adults, with 39% of adults >60 yr. The female/male ratio was 1.9. At presentation, the mean 24-h urine protein was 4.6 g, nephrotic syndrome was present in 33%, renal insufficiency in 59%, and hematuria in 87% of patients. Compared with adults, children had lower incidence of renal insufficiency and were more likely to have reduced C3. Histologic pattern included membranoproliferative, mesangial, endocapillary, and crescentic glomerulonephritis. Treatment included immunosuppression (IS) alone in seven, renin angiotensin system (RAS) blockade alone in six, and combined IS/RAS blockade in 11. On follow-up (mean 63 mo) available in 27 patients, 26% had complete response, 48% had persistent renal dysfunction, and 26% had ESRD. Correlates of ESRD were older age and higher creatinine at biopsy, the absence of combined IS/RAS blockade therapy and the presence of subepithelial humps, but not histologic pattern. On multivariate analysis, age and creatinine emerged as the only independent predictors of ESRD. CONCLUSIONS: DDD is clinically and pathologically heterogeneous. Adults have worse outcome than children, despite similar treatment. Combined IS/RAS blockade appears superior to either agent alone.

Radical cystectomy in patients aged > or = 75 years: an updated review of patients treated with curative and palliative intent.

OBJECTIVE: To evaluate the morbidity and mortality of radical cystectomy in a group of unselected patients aged > or = 75 years who were treated with curative and palliative intent. PATIENTS AND METHODS: We retrospectively analysed 53 patients aged 75-90 years (median 78.8 years) who had radical cystectomies between May 1994 and July 2002. The patients were divided into two groups: 46 were treated with curative intent (group A) and seven with palliative intent (group B). The indications for cystectomy in group A were recurrent and otherwise therapy-resistant bladder cancer, severe irritative voiding symptoms, and recurrent macrohaematuria. The indications in group B were advanced pelvic malignancy with severe irritative voiding symptoms, severe pain, and recurrent macrohaematuria requiring blood transfusions. Patients were categorized according to the American Society of Anesthesiologists classification, with a score of II in 28 patients, III in 21 and IV in four. Complications and mortality before, during and after surgery, and the duration of hospital stay and clinical outcome, were assessed. RESULTS; The early mortality rate in group A was 4% (2/46); in group B two patients died after prolonged complications. The median (range) hospital stay was 28 (6-56) days, and was significantly longer in patients with complications, at a median (range) of 36 (6-70) days. The complication rates early and late after surgery in group A were 22% and 11%, respectively, and in group B, five of seven (early). The total median survival was 2 (0.33-7) years. CONCLUSIONS: Elderly people undergoing radical cystectomy have a greater risk of perioperative morbidity and mortality, especially those with very advanced pelvic malignancies who have had cystectomy with palliative intent. The incidence of early and late complications in patients treated with curative intent is acceptable, but the hospital stay is prolonged.

Impact of interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphism on IgA nephropathy.

BACKGROUND: It is evident that cytokines play an important role in the pathogenesis as well as disease progression in IgA nephropathy (IgAN). The level of cytokine production is influenced by different genotypes that reflect gene polymorphism of the pertinent cytokine. Interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor-alpha (TNF-alpha) gene polymorphism have been found to affect disease susceptibility and activity in several inflammatory diseases. However, the impact of these polymorphisms in IgAN patients has not previously been thoroughly studied. METHODS: We investigated 111 cases of biopsy-proven IgAN and 100 healthy, normal controls for their IL-1ra and TNF-alpha gene polymorphism. IL-1ra gene polymorphism was characterized as a variable number of tandem repeats of a 86 bp sequence within intron 2. Five alleles were identified and were designated as IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5, corresponding to 4, 2, 5, 3, 6 repeats, respectively. A polymorphism in the promoter region of the TNF-alpha gene was also studied. This polymorphism involved a guanidine to adenosine transition at position -308 and was designated as TNF1 (-308G) and TNF2 (-308A). RESULTS: There were 54 male and 57 female patients with a mean age of 30.3 +/- 12.5 years and a disease duration of 66. 8 +/- 47.2 months. The mean duration of the follow-up period was 47. 3 +/- 32.6 months. In the patient group, the allele frequencies of IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5 were 89.6%, 9.9%, 0%, 0.5%, and 0%, respectively, whereas the corresponding carriage rates were 100%, 19.8%, 0%, 0.9%, and 0%, respectively. An excessive carriage of IL2RN*2 was found in the patients when compared with normal controls (allele frequency, 9.9 vs. 2.5%, P < 0.0001). The allele frequencies of TNF1 and TNF2 were 94.1 and 5.9%, respectively, and the carriage rates were 99.1 and 10.8%, respectively, in the patients, which was not significantly different from those of normal controls. When the patients were stratified into mild and severe groups according to their initial presentation, none of the studied alleles correlated with the severity. However, patients with gross hematuria were associated with a higher carriage rate of TNF2 when compared with patients without gross hematuria (allele frequency, 15. 4 vs. 4.6%, P = 0.0552; carriage rate, 30.8% vs. 8.2%, P = 0.0272). Renal survival analysis revealed that the TNF2 carrier had a renal survival comparable with TNF2 (-) patients. However, the carriage of the IL1RN*2 allele was associated with a significantly poorer long-term outcome with a median survival time of 72 months, as compared with those without IL1RN*2 (134 months, P < 0.01). CONCLUSION: IL-1ra and TNF-alpha gene polymorphism may affect disease susceptibility as well as disease activity and long-term outcome in human IgAN. Treatment with an IL-1ra or IL-1 blocking agent may be relevant in those carrying the IL1RN*2 allele.

Hemorrhagic cystitis in bone marrow transplantation.

OBJECTIVES: Patients undergoing bone marrow transplantation are at risk for hemorrhagic cystitis despite appropriate preventive measures. This complication could have an impact on patient survival and other outcome variables. METHODS: A retrospective study of patients subjected to bone marrow transplantation was conducted to determine risk factors for hemorrhagic cystitis and evaluate the impact of hemorrhagic cystitis on certain outcome variables. Patients who experienced hemorrhagic cystitis received various forms of therapy, at the discretion of the treating physician. RESULTS: Hemorrhagic cystitis occurred more frequently in younger patients and those undergoing allogeneic transplantation. The occurrence of hemorrhagic cystitis was associated with increased hospital costs, length of hospitalization, and mortality. Gender, race, type of malignancy, other pretransplantation comorbidity, and the occurrence of other peritransplantation complications were not associated with occurrence of hemorrhagic cystitis. CONCLUSIONS: Hemorrhagic cystitis is a significant complication of bone marrow transplantation, which influences economic and survival outcome. Since the number of bone marrow transplants being performed is increasing, urologists should be prepared to play an active role in treating patients who experience this complication.