Pyuria, urinary tract infection and renal outcome in patients with chronic kidney disease stage 3-5.

Pyuria is common in chronic kidney disease (CKD), which could be due to either urinary tract infection (UTI) or renal parenchymal inflammation. Only little is known regarding the association of pyuria or UTI with renal outcomes. We investigated 3226 patients with stage 3-5 CKD. Pyuria was defined as ≥ 50 WBC per high-power field (hpf) and was correlated to old age, female, diabetes, hypoalbuminemia, lower eGFR, and higher inflammation status. In Cox regression, patients with more than one episode of pyuria in the first year (11.8%) had increased risks for end-stage renal disease (ESRD) [hazard ratio (95% CI): 1.90 (1.58-2.28); p < 0.001], rapid renal function progression [odds ratio (95% CI): 1.49 (1.13-1.95); p = 0.001], and all-cause mortality [hazard ratio: 1.63 (1.29-2.05); p < 0.001], compared to those without pyuria. In a subgroup analysis, the risk of pyuria for ESRD was modified by CKD stages. We investigated the effects of UTI (urinary symptoms and treated by antibiotics) and pyuria without UTI (urine WBC < 50 to ≥ 10/hpf without any episodes of ≥ 50 WBC/hpf or UTI), while both groups were associated with clinical outcomes. In conclusion, CKD stage 3-5 patients with frequent pyuria or UTI episodes have increased risks of renal outcomes.

Recalcitrant chronic bladder pain and recurrent cystitis but negative urinalysis: What should we do?

PURPOSE: Lower urinary tract symptoms (LUTS) may be associated with chronic urinary tract infection (UTI) undetected by routine diagnostic tests. Antimicrobial therapy might confer benefit for these patients. MATERIALS AND METHODS: Over 10 years, we treated patients with chronic LUTS. Pyuria was adopted as the principal biomarker of infection. Urinary leucocyte counts were recorded from microscopy of fresh midstream urine (MSU) samples. Antibiotics were prescribed and the prescription adjusted to achieve a measurable clinical response and a reduction in pyuria. RESULTS: We treated 624 women [mean age = 53.4 years; standard deviation (SD) = 18] with chronic LUTS and pyuria. Mean duration of symptoms prior to presentation was 6.5 years. Only 16% of MSU cultures submitted were positive (≥105 cfu ml-1). Mean treatment length was 383 days [SD = 347; 95% confidence interval (CI) = 337-428]. Treatment was associated with a reduction in total LUTS (F = 98; p = 0.0001), 24-h frequency (F = 75; p = 0.0001), urinary urgency (F = 90; p = 0.0001), lower urinary tract pain (F = 108; p = 0.0001), voiding symptoms (F = 10; p = 0.002), and pyuria (F = 15.4; p = 0.0001). Full-dose first-generation antibiotics for UTI, such as cefalexin, nitrofurantoin, or trimethoprim, were combined with methenamine hippurate. We recorded 475 adverse events (AEs) during 273,762 treatment days. There was only one serious adverse event (SAE). We observed no increase in the proportion of resistant bacterial isolates. CONCLUSION: This large case series demonstrates that patients with chronic LUTS and pyuria experience symptom regression and a reduction in urinary tract inflammation associated with antimicrobial therapy. Disease regression was achieved with a low frequency of AEs. These results provide preliminary data to inform a future randomized controlled trial (RCT).

Urinary ATP as an indicator of infection and inflammation of the urinary tract in patients with lower urinary tract symptoms.

BACKGROUND: Adenosine-5'-triphosphate (ATP) is a neurotransmitter and inflammatory cytokine implicated in the pathophysiology of lower urinary tract disease. ATP additionally reflects microbial biomass thus has potential as a surrogate marker of urinary tract infection (UTI). The optimum clinical sampling method for ATP urinalysis has not been established. We tested the potential of urinary ATP in the assessment of lower urinary tract symptoms, infection and inflammation, and validated sampling methods for clinical practice. METHODS: A prospective, blinded, cross-sectional observational study of adult patients presenting with lower urinary tract symptoms (LUTS) and asymptomatic controls, was conducted between October 2009 and October 2012. Urinary ATP was assayed by a luciferin-luciferase method, pyuria counted by microscopy of fresh unspun urine and symptoms assessed using validated questionnaires. The sample collection, storage and processing methods were also validated. RESULTS: 75 controls and 340 patients with LUTS were grouped as without pyuria (n = 100), pyuria 1-9 wbc µl(-1) (n = 120) and pyuria ≥10 wbc µl(-1) (n = 120). Urinary ATP was higher in association with female gender, voiding symptoms, pyuria greater than 10 wbc µl(-1) and negative MSU culture. ROC curve analysis showed no evidence of diagnostic test potential. The urinary ATP signal decayed with storage at 23°C but was prevented by immediate freezing at ≤ -20°C, without boric acid preservative and without the need to centrifuge urine prior to freezing. CONCLUSIONS: Urinary ATP may have a role as a research tool but is unconvincing as a surrogate, clinical diagnostic marker.

Do patients who complain of lower urinary tract symptoms frequently have clinically significant pyuria?

There is still controversy about whether post-void residual (PVR) urine volume affects the onset of urinary tract infection (UTI). In addition, although male patients with lower urinary tract symptoms (LUTS) might potentially have PVR, the association between LUTS and UTI or asymptomatic pyuria with or without bacteriuria remains unclear. We studied the frequency of asymptomatic pyuria, with and without bacteriuria, in patients with LUTS without a previous history of urinary tract manipulation at the first visit and their sequential courses. This retrospective study was done by reviewing medical charts. A total of 453 male patients who complained of LUTS and visited our outpatient clinic in 2008 were included in this study. The frequency of pyuria, with or without bacteriuria, in this study at the first visit was 4.9%. The median PVR volumes at the initial examination were 79 ml in the 22 patients with pyuria and 22 ml in the 431 patients without pyuria. The difference of the PVR volume between the patients with pyuria and those without pyuria was statistically significant (p = 0.0095). Twelve patients were treated with alpha-blockers without antimicrobial chemotherapy and pyuria disappeared in 5 (41.7%) of them. However, the decrease in the rate of PVR was not significantly different between the patients with persisting pyuria and those without pyuria. A not negligible number of patients with LUTS had pyuria at the first visit; however, there was no febrile UTI in their clinical course even if they received no urological manipulation.

What is the role of covert infection in detrusor overactivity, and other LUTD? ICI-RS 2013.

A think tank was convened at the fourth ICI-RS meeting, which took place June 5-7, 2013 in Bristol UK, to consider current evidence and controversies surrounding the possible role of 'covert infection' in the pathophysiology of refractory detrusor overactivity (DO) and other lower urinary tract disorders (LUTD). The topic was chosen because several authors from different centers worldwide have recently published evidence which supports this concept. However, to date there is inconsistency regarding terminology and microbiological definitions, which were discussed by the participants. The mechanisms whereby infection/inflammation could actually promote aberrant detrusor contractions in the human remain controversial, and are more fully described in this report. Future requirements for research into this topic were outlined.

[Kidney function in oncologic patients after cisplastin chemotherapy].

During examination of kidney function under cisplastin chemotherapy in oncologic patients the nephrotoxicity of the drug have been shown during 24 hours after administration. We found that in 24 hours after injection ofcisplastin in the dose 50 mg/m2 of the surface of the body, the excretion of creatinine, sodium, potassium, osmotic active compounds and chlorides is increased more than two times, indicating for disorder in osmolality, volume and ionic regulation of kidney function. The determined peculiarities are consequences of kidney injuries, which are confirmed by an increase in erythrocyte- and leucocyteuria. We showed that alterations in homeostatic kidney function is due to damage of renal tubules. Our study necessitates a need for renal protection during the whole period of cisplastin chemotherapy.

Pyuria in patients treated with indinavir is associated with renal dysfunction.

BACKGROUND: Indinavir therapy is associated with a continuum of crystal-related syndromes, including nephrolithiasis, renal colic, flank pain without recognizable stone formation, dysuria and asymptomatic crystalluria. A frank nephropathy has been recognized recently as part of the spectrum. METHODS: A retrospective analysis of 72 HIV-infected individuals receiving indinavir was performed to identify the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals treated with nucleoside analogues alone served as controls. RESULTS: Mean serum creatinine levels rose from 1.03 +/- 0.16 mg/dl to 1.11 +/- 0.22 mg/dl at week 12 and 1.15 +/- 0.27 mg/dl at week 24 (both, p < 0.01). Thirteen individuals developed serum creatinine levels > or =1.4 mg/dl. Increased serum creatinine levels were found more frequently in women (p < 0.01) and were associated with pyuria and microhematuria (p < 0.01). Frank renal colic and/or nephrolithiasis (seven patients) and urinary pH were not associated with serum creatinine levels > or =1.4 mg/dl. The mean duration of indinavir treatment, until sterile pyuria occurred, were 22 weeks and 32 weeks until the first rise of serum creatinine levels to > or =1.4 mg/dl. Ten patients showed both findings, pyuria preceded the first rise in serum creatinine levels to > or = 1.4 mg/dl (18 vs. 27 weeks, p = 0.02). Renal biopsy, done in three patients, revealed tubulointerstitial disease with crystals in collecting ducts. In 21 patients, among them 11 with pyuria, indinavir was replaced for various reasons and pyuria disappeared in nine. In these patients mean serum creatinine levels decreased from 1.43 mg/dl at withdrawal of indinavir to 1.04 mg/dl three months later (p < 0.01). CONCLUSION: Indinavir therapy is associated with a decrease in renal function which is reversible after withdrawal. In addition, indinavir-associated tubulointerstitial disease does no in patients taking indinavir may help to identify patients being at risk for nephrotoxicity.

Urological abnormalities in 1,328 patients with nocturnal enuresis.

OBJECTIVES: Evaluation of the incidence of urological abnormalities as revealed by urological examinations of a large number of patients with enuresis. METHODS: Patients with the chief complaint of nocturnal enuresis were examined urologically. RESULTS: The incidence of urological abnormalities was 1.8% of 940 patients on intravenous pyelography (IVP), 7.1% of 695 patients on voiding cystourethrography (VCG) and 11.5% of 487 patients on cystometry (CM). No abnormal findings were observed in 58 patients on renal ultrasonography (US). 92.1% of reflux cases detected by VCG were low grade and only 8.9% of patients with reflux had pyuria. 20.2% of 446 patients who were submitted to all these examinations had some urological abnormality. Only pollakisuria was statistically more frequent in patients with urological abnormalities than in patients without them. CONCLUSION: These data suggest that the incidence of urological abnormalities was rather low when compared with the past literature. In particular, IVP was though to be unnecessary.

Association of sexual activity and bacteriuria in women with non-insulin-dependent diabetes mellitus.

A group of 215 patients with non-insulin-dependent diabetes mellitus (NIDDM) (147 women and 68 men) were selected by home interview, and accepted to undergo clinical examination including urine culture, in order to determine the frequency of bacteriuria and its possible associations with clinical and laboratory findings. Bacteriuria was found in 17.7% of women and 1.5% of men. Univariate and multivariate analysis performed for the group of women revealed sexual intercourse and pyuria as the only factors associated with the frequency of bacteriuria. It was concluded that asymptomatic bacteriuria may be associated with sexual activity in women with NIDDM.

[Vesicourethral dysfunction of diabetic patients].

In order to evaluate vesicourethral dysfunction in diabetic patients, urodynamic studies, IVP and urinalysis were performed on 173 diabetic patients (male 78, female 95) and 17 nondiabetic control cases. In addition to the classical findings as increased volume at the first desire to void and decreased maximum vesical pressure, diabetic patients showed varieties of vesicourethral dysfunctions such as overactive bladder (14.5%), low compliance bladder (11.0%) and loss of detrusor-external sphincter coordination (31.7%). Vesicourethral function of diabetics was classified in following 5 types by analysing the volume at first desire to void, volume at maximum desire to void, maximum vesical pressure, residual urine volume and bladder compliance. 1. Type 1, normal vesical function, 13 cases. 2. Type 2, vesical dysfunction with minimal residual urine, 49 cases. 3. Type 3, vesical dysfunction with residual urine, 66 cases. 4. Type 4, low compliance bladder, 20 cases. 5. Type 5, overactive bladder, 25 cases. Pyuria was observed in 59.8%, hydronephrosis was found in 10.9% and ectasia of lower ureter was found in 17.8% of diabetic patients. The highest incidence of pyuria and abnormality of the upper urinary tract were noted in Type 4 and followed by Type 3 and by Type 2 in decreasing order. Extent of pyuria and ectasis of the upper urinary tract showed statistically significant correlation with residual urine volume and detrusor-external sphincter coordination. When vesicourethral function was compensated by abdominal strain, the volume of residual urine is not elevated, but when the mechanism of compensation is lost or in the absence of detrusor-external sphincter coordination results in gradual accumulation of residual urine. In cases with long standing chronic urinary tract infection may results in fibrosis of the bladder wall with low compliance bladder. Fibrotic obstruction of uretero-vesical junction can cause hydroureteronephrosis and followed by renal function impairment. As vesical damage become irreversible at this end stage, proper management during early stage is crucial for management of diabetic patients. Cholinergic agent were effective to reduce residual urine volume in Type 3. alpha-blocking agent were effective to reduce residual urine volume in Type 3 and some cases of Type 4. In cases in which medication therapy failed to reduce residual urine, the clean intermittent catheterization was successful in control of urinary tract infection and upper urinary tract ectasis. Transurethral resection of the prostate and the bladder neck is indicated in the male patients with a large amount of residual urine in Type 3 and 4.