**1. Introduction**

376 Chronic Kidney Disease

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Chronic Kidney Disease and Associated Risk Factors --- United States, 1999--2004."

hyperplasia is related to the percent area density of prostate smooth muscle."

retention of urine: the relationship between detrusor activity and upper tract

elderly due to abnormalities of the lower urinary tract and ureterovesical junction."

prostate and transition zone size with symptom score, bother score, urinary flow

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novel, minimally invasive treatment for lower urinary tract symptoms (LUTS)

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small residual urine volumes in patients with benign prostatic hyperplasia."

Nakatani, T. (2010). "Association between chronic kidney disease and small residual urine volumes in patients with benign prostatic hyperplasia." *Nephrology*  Chronic kidney disease is an increasing public health problem. In the United States, the prevalence is estimated to be approximately 11% of the adult population. Chronic kidney disease may progress to end-stage renal failure, a condition associated with high morbidity and mortality. Diabetes mellitus (DM) is one of the main causes of kidney disease and endstage renal failure. In the United States, DM is the primary diagnosis in 44% of all new cases of renal replacement therapy. Vascular complications are the most common cause of diabetic nephropathy, but it is possible that urinary tract infections (UTIs) also contribute to renal insufficiency in patients with DM.

The urinary tract is normally sterile. However, asymptomatic bacteriuria (ASB), which is defined as the presence of a positive urine culture with at least 10e5 cfu/ml collected from a patient without symptoms of a UTI, is a common phenomenon, especially in women. Different studies report a prevalence of approximately 1-5% among healthy young women, increasing to over 20% in the elderly and 12-26% in women with DM. A Swedish study among 1,462 adult women showed that women with bacteriuria at study entry had an increased risk of having bacteriuria six and twelve years later, compared to women without bacteriuria (Odds Ratio (OR) 6.9 and 3.1, after six and twelve years, respectively). Another Swedish study among 116 schoolgirls with ASB showed that at baseline renal parenchymal reduction was found in 10.3%, while reflux was found in 20.7%, but only 30% of the 116 patients had a history referable to an earlier UTI. A 3-year follow-up of these 116 schoolgirls with ASB (treated or untreated) showed that the risk of developing renal damage as a result of ASB in a schoolgirl with a roentgenographically normal urinary tract seemed to be small.

*Escherichia coli* is the most prevalent causative microorganism in both symptomatic and asymptomatic bacteriuria, accounting for more than 80% of uncomplicated UTIs. Previous studies have demonstrated that patients with renal scarring due to pyelonephritis are at increased risk for the development of hypertension and chronic kidney disease. Results from previous in vitro and in vivo studies indicate that a UTI with *E. coli* can lead to renal damage, either by the microorganism itself or by the following host response. For instance, it has been shown that type 1 fimbriae (the adhesive organelles at the outer surface of the bacterial

Asymptomatic Bacteriuria (ASB), Renal Function and Hypertension 379

distribution in stages of renal function was not different for women with bacteriuria

no (n=442) yes (n=48) **E.coli-bacteriuria**

Fig. 1. Differences in creatinine clearance between women WITHOUT DM with and without ASB. (Meiland R, Stolk RP, Geerlings SE, Peeters PH, Grobbee DE, Coenjaerts FE, Brouwer EC, Hoepelman AI. Association between *Escherichia coli* bacteriuria and renal function in

To obtain follow-up information on end-stage renal failure, we obtained data from the Renal Replacement Registry Netherlands (RENINE) that were available May 2002. RENINE is a foundation in which all Dutch nephrologists participate and where patients are registered who at one time have used kidney replacing therapy (hemodialysis or renal transplantation), with a coverage rate throughout the years of nearly 100%. Data from the baseline cohort and RENINE were matched on (maiden and married) name combined with date of birth to select the cases. A group consisting of four times the number of cases was randomly selected from the baseline cohort to form the control group. Four women participated in the follow-up cohort and were also selected as one of the cases who received kidney replacing therapy during follow-up; one woman underwent kidney transplantation before blood withdrawal (and was excluded for the cohort analysis), three women developed end-stage renal failure thereafter (and were included in both analyses). After excluding four individuals with a missing urine sample 49 cases and 206 controls were included. Among the cases, the mean duration until the date of kidney replacing therapy was 13.8 ± 7.4 years, with a minimum and maximum duration of 1.6 and 25.5 years, respectively. In the control group, the mean follow-up (i.e. the time from participation in the

women: long-term follow-up. Arch Intern Med. 2007 Feb 12;167(3):253-7.)

baseline cohort until study-endpoint in May 2002) was 27.0 ± 0.2 years.

compared to women without bacteriuria.

0

**2.3 Nested case-control study population** 

30

60

90

**creatinine clearance (mL/min)**

120

150

membrane) can cause scarring in the renal parenchyma of rats, with large foci of inflammation. This might be due to the activation of polymorphonuclear leukocytes by type 1 fimbriatedstrains, which leads to the release of tissue destroying enzymes. Mice models have shown that although neutrophils are important in bacterial clearance, they can also cause renal damage.

In a clinical study, renal scarring was detected in 29 of 63 adult women ten to twenty years after hospitalization for pyelonephritis. In contrast, no study has convincingly shown that ASB can lead to a clinically relevant decline in renal function in otherwise healthy women. Several authors in the first half of the twentieth century have suggested a role of bacteriuria in the etiology of hypertension, but the pathogenesis is not understood.
