Weight loss reduces the incidence of dipstick proteinuria: a cohort study from the Japanese general population

Clinical and Experimental Nephrology - Though elimination of obesity is one of main therapeutic goal for lifestyle-related diseases, the impact of appropriate weight loss on reduction of the...     

Dipstick proteinuria and all-cause mortality among the general population

Background

Dipstick proteinuria, but not albuminuria, is used for general health screening in Japan. How the results of dipstick proteinuria tests correlate with mortality and, however, is not known.

Methods

Subjects were participants of the 2008 Tokutei-Kenshin (Specific Health Check and Guidance program) in six districts in Japan. On the basis of the national database of death certificates from 2008 to 2012, we used a personal identifier in two computer registries to identify participants who might have died. The hazard ratio (95% confidence interval, CI) was calculated by Cox-proportional hazard analysis.

Results

Among a total of 140,761 subjects, we identified 1641 mortalities that occurred by the end of 2012. The crude mortality rates were 1.1% for subjects who were proteinuria (?), 1.5% for those with proteinuria (+/?), 2.0% for those with proteinuria (1+), 3.5% for those with proteinuria (2+), and 3.7% for those with proteinuria (≥?3+). After adjusting for sex, age, body mass index, estimated glomerular filtration rate, comorbid condition, past history, and lifestyle, the hazard ratio (95% CI) for dipstick proteinuria was 1.262 (1.079–1.467) for those with proteinuria (+/?), 1.437 (1.168–1.748) for those with proteinuria (1+), 2.201 (1.688–2.867) for those with proteinuria (2+), and 2.222 (1.418–3.301) for those with proteinuria (≥?3+) compared with the reference of proteinuria (?).

Conclusion

Dipstick proteinuria is an independent predictor of death among Japanese community-based screening participants.

     

Clinical utility of trace proteinuria for microalbuminuria screening in the general population

Background The urine dipstick test that regards > 1+ proteinuria as positive is unsuitable for microalbuminuria screening owing to its low sensitivity in the general population. We conducted a cross-sectional survey to examine whether trace proteinuria could be an indicator of microalbuminuria. Methods The subjects were 2321 participants in a community-based health check-up in Takahata, Japan. Dipstick tests for proteinuria and the urine albumin–creatinine ratio (UACR) measurement were performed with single-spot urine specimens collected early in the morning. The results of the dipstick tests were recorded as (−), trace, (1+), (2+), and (3+). Micro- and macroalbuminuria were defined as UACR 30–300 mg/g and > 300 mg/g, respectively. Results Overall, the prevalence and median UACR levels of urine protein (−), trace, (1+), (2+), and (3+) were 92.0% (8.8 mg/g), 3.5% (43 mg/g), 2.6% (81 mg/g), 1.4% (315 mg/g), and 0.5% (1073 mg/g), respectively. Within the trace proteinuria category, the prevalence of microalbuminuria in all subjects, men, subjects ≥60 years, diabetic subjects, and hypertensive subjects was 59.3%, 73.8%, 71.2%, 88.9%, and 68.0%, respectively. By regarding trace proteinuria as positive, the sensitivity of the urine protein dipstick test for micro- and macroalbuminuria was improved (from 23.3% to 37.1%), while its specificity was not significantly changed (from 98.9% to 97.3%). Conclusion Trace proteinuria could be a useful indicator of microalbuminuria in the general population, and especially in subjects at high risk of cardiovascular disease.     

Declining incidence of persistent proteinuria in type I (insulin-dependent) diabetic patients in Denmark

The decreasing relative mortality among type I (insulin-dependent) diabetic patients during the last 50 years might be related to the incidence of clinical diabetic nephropathy. We therefore followed 2890 type I diabetic patients (1607 males and 1283 females) diagnosed between 1933 and 1972 and before the age of 31, from admission to death, emigration, or January 1, 1984. All patients had been admitted to the Steno Memorial Hospital. Information on development of proteinuria was obtained in 2658 patients (92%). Five hundred twenty-five patients developed proteinuria due to diabetes and 49 developed nondiabetic proteinuria. When comparing patients diagnosed between 1933 and 1942 with those diagnosed between 1953 and 1962, the incidence of proteinuria decreased by 30% (P less than .03). This might explain the decrease of relative mortality in type I diabetic patients. The incidence decreased with increasing age at onset but was always highest in males. Insulin dose (U/kg) and diabetes duration at admission did not influence the incidence of proteinuria. The incidence peaked after 15-17 yr of diabetes duration independent of sex, age at diagnosis, or calendar year of diagnosis. However, the majority of patients did not develop proteinuria during 40 yr of diabetes. This suggests individual renal susceptibility to the deleterious effect of hyperglycemia.     

Association between albuminuria and proteinuria in the general population: the AusDiab Study.

BACKGROUND: The relationship between urinary albumin and total protein excretion and the appropriateness of one test over the other are unclear due to the paucity of large epidemiological studies of albuminuria and proteinuria. In screening for renal and cardiovascular disease, whether to measure albuminuria, proteinuria or both, is currently an unanswered question. METHODS: Random urine samples from 10,596 (94.2%) participants of the Australian Diabetes, Obesity and Lifestyle Study were tested for albuminuria (urine albumin:creatinine > or =30 mg/g) and proteinuria (urine protein:creatinine > or =0.20 mg/mg). This study was a representative sample of the national non-institutionalized population drawn from 42 randomly selected urban and non-urban areas (census collector districts) across Australia. RESULTS: Among a representative cross-section of the Australian adult population, urine albumin excretion was strongly correlated with total protein excretion, particularly among the elderly, and those with diabetes mellitus, hypertension, obesity and renal impairment (P <0.001). Albuminuria performed well as a screening test for proteinuria: sensitivity 91.7% [95% confidence interval (CI) 87.7-94.5%], specificity 95.3% (95% CI 94.9-95.7%) and negative predictive value 99.8% (95% CI 99.7-99.9%). However, among those with proteinuria, 8% excreted albumin within the normal range. CONCLUSIONS: While albuminuria may be a suitable test for general population screening for renal and cardiovascular disease, it should not replace testing for proteinuria in those with known or suspected renal disease.     

Effects of current smoking and smoking discontinuation on renal function and proteinuria in the general population

BACKGROUND: Smoking may adversely affect the progression of renal diseases. However, it is unknown whether smoking affects renal function in subjects without nephropathy. METHODS: In 1998, 28,409 volunteers from the general population were examined at the Institut Régional pour la Santé (IRSA). Renal function was estimated with creatinine clearance using the Cockcroft formula. Dipstick proteinuria was assessed on an overnight urine sample by a trained technician. RESULTS: Adjusted creatinine clearance was higher in current smokers than in former smokers and never smokers (100.6 +/- 13.6 vs. 98.8 +/- 13.9 mL/min/1.73 m2, P < 0.0001, and vs. 98.5 +/- 14.0 mL/min/1. 73 m2, P < 0.0001, respectively). This difference was predominant in men and weak in women, and was associated with the number of cigarettes smoked daily. The slope of the projected age-related decline in the creatinine clearance accelerated with age, but it was similar in current smokers, former smokers, and never smokers. Creatinine clearance was associated with a relative risk of proteinuria [for each mL/min/1.73 m2, the relative risk was 1.007 (95% CI, 1.000 to 1.015), P = 0.056, for 1+ or higher proteinuria; and 1.018 (1.004 to 1.030), P = 0.0078, for 2+ or higher proteinuria]. Current and former smokers had a marked risk of 2 or higher proteinuria [adjusted RR (95% CI), 3.26 (1.66 to 6.80), P = 0. 0009, and 2.69 (1.24 to 5.99), respectively, P = 0.013, vs. never smoking], which was independent of the daily or cumulative cigarette consumption. CONCLUSIONS: In the general population, smokers do not exhibit lower creatinine clearance than never smokers. In fact, creatinine clearance is slightly higher in current smokers at least in men, even when normotensive and hypertensive subjects are analyzed separately, but the difference is small, especially in women. This effect seems reversible upon smoking discontinuation. Chronic smoking results in a marked risk of irreversible proteinuria that may occur despite moderate smoking.     

Alcohol consumption and incidence of proteinuria: a retrospective cohort study

Background

Previous studies report conflicting results of a dose-dependent association between alcohol consumption and incidence of chronic kidney disease. Only a few studies have assessed the clinical impact of >?45–65 g/day of critically high alcohol consumption.

Methods

This retrospective cohort study included 88,647 males and 88,925 females with dipstick urinary protein?≤?±?and estimated glomerular filtration rate?≥?60 mL/min/1.73 m² at their first annual health examinations between April 2008 and March 2010 in Japan. The exposure was the self-reported alcohol consumption. The outcome was proteinuria defined as dipstick urinary protein?≥?1?+?or ≥?2?+.

Results

During median 1.8 years (interquartile range 1.0–2.1) of the observational period, 5416 (6.1%) males and 3262 (3.7%) females developed proteinuria defined as dipstick urinary protein?≥?1?+. In males, a U-shape association between alcohol consumption and proteinuria was observed in a multivariable-adjusted Poisson regression model [incidence rate ratio (95% confidence interval) of rare, occasional, and daily drinkers with ≤?19, 20–39, 40–59, and ≥?60 g/day: 1.00 (reference), 0.86 (0.79–0.94), 0.70 (0.64–0.78), 0.82 (0.75–0.90), 1.00 (0.90–1.11), and 1.00 (0.85–1.17), respectively], whereas a J-shape association was observed in females [1.00 (reference), 0.81 (0.75–0.87), 0.74 (0.64–0.85), 0.93 (0.78–1.11), 1.09 (0.83–1.44), and 1.45 (1.02–2.08), respectively]. Similar associations with dipstick urinary protein?≥?2?+?were shown in males and females.

Conclusions

Moderate alcohol consumption was associated with lower risk of proteinuria in both males and females. Females with ≥?60 g/day of high alcohol consumption were at higher risk of proteinuria, whereas males were not. Females were more vulnerable to high alcohol consumption, than males.

     

U-shaped association between body mass index and proteinuria in a large Japanese general population sample

Background

There is little data on the association between body mass index (BMI) and proteinuria.

Methods

This was a cross-sectional cohort study assessing the association between BMI and proteinuria in a large Japanese population. Using a nationwide health check-up database of 212,251 Japanese aged >20 years with no pre-existing cardiovascular diseases (185,183 men, median age 66 years; 127,068 women, median age 65 years), we examined the association between BMI and proteinuria (≥1+ on dipstick).

Results

Subjects were divided into 11 subgroups by BMI grading in 1 kg/m² intervals from 18.5?27.5 kg/m². A BMI of approximately 22 ± 0.5 kg/m² was considered optimal for Japanese; therefore, this subgroup was set as a reference when logistic analysis was applied. Age, waist circumference, height, weight, smoking and drinking habits, use of medications such as antihypertensive, antidiabetic, or antihyperlipidemic, as well as proteinuria, estimated glomerular filtration rate (eGFR), chemistry data, and blood pressure levels were significantly different between subgroups in both genders. The odds ratio for proteinuria showed a U-shape in men and women, even after adjustment for significant covariates such as age, waist circumference, systolic blood pressure, eGFR, fasting plasma glucose, triglyceride, low-density lipoprotein, antihypertensive use, antidiabetic use, antihyperlipidemic use, and lifestyle factors (smoking and drinking). Gender differences were also prominent—a BMI <20.4 kg/m² was significantly associated with proteinuria in men compared to a BMI <18.4 kg/m² in women. On the other hand, a BMI ≥ 25.5 kg/m² was also significantly associated with proteinuria in men compared to a BMI ≥ 22.5 kg/m² in women.

Conclusions

We found that BMI levels were associated with proteinuria in a U-shaped manner and showed marked gender differences. Health guidance should not only focus on higher BMI subjects, but also on thin subjects, in terms of the prevention of chronic kidney disease.     

Low incidence of acute urinary retention in the general male population: the triumph project

OBJECTIVE: To describe the incidence of acute urinary retention (AUR) in the general male population and in a population of men newly diagnosed with lower urinary tract symptoms suggestive of BPH (LUTS/BPH). METHODS: We performed a retrospective cohort study in the Integrated Primary Care Information (IPCI) database, a GP research database in The Netherlands, during the period 1995-2000. All males, > or =45 years, without a history of AUR or radical cystectomy were included in the study. In addition, we followed a sub-cohort of men, newly diagnosed with LUTS/BPH. AUR was defined as the sudden inability to urinate, requiring catheterization. RESULTS: Amongst 56,958 males with a mean follow-up of 2.8 years, 344 AUR cases occurred (incidence rate 2.2/1000 man-years) of whom more than 40% were precipitated. AUR was the first symptom of LUTS/BPH in 73 (49%) of the 149 AUR cases that occurred in men newly diagnosed with LUTS/BPH. The risk of AUR was 11-fold higher in patients newly diagnosed with LUTS/BPH (RR 11.5; 95%CI: 8.4-15.6) with an overall incidence rate of 18.3/1000 man-years (95%CI: 14.5-22.8). CONCLUSIONS: The incidence rate of AUR is low in the general population but substantial in a population of men newly diagnosed with LUTS/BPH. The incidence rate increases with age and AUR is precipitated in approximately 40% of all cases. Within the LUTS/BPH cohort, AUR is the first presenting symptom of BPH in 50% of all AUR cases.     

Epidemiology of persistent proteinuria in type II diabetes mellitus. Population-based study in Rochester, Minnesota

Clinical risk factors for nephropathy were assessed in a population-based study of Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort). The 1031 Rochester residents with non-insulin-dependent diabetes mellitus (NIDDM) were followed through their complete medical records in the community to 1 January 1982. The prevalence of persistent proteinuria was 8.2% at the diagnosis of NIDDM. Among those initially free of persistent proteinuria, the subsequent incidence was 15.3/1000 person-yr. Twenty years after the diagnosis of diabetes, the cumulative incidence of persistent proteinuria was 24.6%. A proportional hazards model identified the following risk factors for persistent proteinuria in NIDDM: elevated initial fasting blood glucose (P less than .01); older age at onset of diabetes (P less than .01); male gender (P = .05); and presence of macrovascular disease (P = .05), diabetic retinopathy (P = .05), or glycosuria (P = .07) at the diagnosis of diabetes. Separate analyses controlling for attained age indicated no association between duration of NIDDM and the incidence of persistent proteinuria. Stratified analysis of the two most significant risk factors (fasting blood glucose and age) indicated that hyperglycemia was a stronger risk factor for proteinuria in younger diabetic subjects, perhaps because of a competing risk of death in the elderly diabetic patient. In contrast to a recently described decreasing secular trend of proteinuria in Danish insulin-dependent diabetes mellitus patients, there was no decrease over the past 40 yr in proteinuria risk in this NIDDM incidence cohort.     

Prostate-specific antigen and long-term prediction of prostate cancer incidence and mortality in the general population

Background

It is largely unknown whether prostate-specific antigen (PSA) level at first date of testing predicts long-term risk of prostate cancer (PCa) incidence and mortality in the general population.

Objective

Determine whether baseline PSA levels predict long-term risk of PCa incidence and mortality.

Design, setting, and participants

We examined 4383 men aged 20–94 yr from the Danish general population in the prospective Copenhagen City Heart Study. PSA was measured in plasma samples obtained in 1981–1983.

Measurements

PCa incidence and mortality as a function of baseline PSA was assessed using Kaplan-Meier plots of cumulative incidence and competing risk subhazard ratios.

Results and limitations

During 28 yr of follow-up, 170 men developed PCa, and 94 men died from PCa. Median follow-up was 18 yr (range: 0.5–28 yr). For PCa incidence, the subhazard ratio was 3.0 (95% confidence interval [CI], 1.9–4.6) for a PSA level of 1.01–2.00 ng/ml, 6.8 (95% CI, 4.2–11) for PSA 2.01–3.00 ng/ml, 6.6 (95% CI, 3.4–13) for PSA 3.01–4.00 ng/ml, 16 (95% CI, 10.4–25) for PSA 4.01–10.00 ng/ml, and 57 (95% CI, 32–104) for PSA >10.00 ng/ml versus 0.01–1.00 ng/ml. For PCa mortality, corresponding subhazard ratios were 2.2 (95% CI, 1.3–3.9), 5.1 (95% CI, 2.8–9.0), 4.2 (95% CI, 1.8–10), 7.0 (95% CI, 3.8–14), and 14 (95% CI, 6.0–32). For men with PSA levels of 0.01–1.00 ng/ml, the absolute 10-yr risk of PCa was 0.6% for ages <45 yr, 0.7% for ages 45–49 yr, 1.1% for ages 50–54 yr, 1.2% for ages 55–59 yr, 1.3% for ages 60–64 yr, 1.1% for ages 65–69 yr, 1.3% for ages 70–74 yr, and 1.5% for ages ≥75 yr; corresponding values for PSA levels >10.00 ng/ml were 35%, 41%, 63%, 71%, 77%, 69%, 75%, and 88%, respectively.

Conclusions

Stepwise increases in PSA at first date of testing predicted a 3–57-fold increased risk of PCa, a 2–16-fold increased risk of PCa mortality, and a 35–88% absolute 10-yr risk of PCa in men with PSA levels >10.00 ng/ml. Equally important, the absolute 10-yr risk of PCa in men with PSA levels 0.01–1.00 ng/ml was only 0.6–1.5%.     

Increasing incidence of proteinuria and declining incidence of end-stage renal disease in diabetic Pima Indians

The introduction of more efficacious treatments for diabetic kidney disease may slow its progression, but evidence for their effectiveness in populations is sparse. We examined trends in the incidence of clinical proteinuria, defined as a urinary protein-to-creatinine ratio >0.5 g/g, and diabetic end-stage renal disease (ESRD), defined as death from diabetic nephropathy or onset of dialysis, in Pima Indians with type 2 diabetes between 1967 and 2002. The study included 2189 diabetic subjects >/=25 years old. During follow-up, 366 incident cases of proteinuria occurred in the subset of 1715 subjects without proteinuria at baseline. The age-sex-adjusted incidence rate of proteinuria increased from 24.3 cases/1000 person-years (pyrs) (95% confidence interval (CI) 18.7-30.0) in 1967-1978 to 35.4 cases/1000 pyrs (95% CI 28.1-42.8) in 1979-1990 and 38.9 cases/1000 pyrs (95% CI 31.2-46.5) in 1991-2002 (P(trend)<0.0002). In each period, the age-sex-adjusted incidence of proteinuria increased with diabetes duration, but diabetes duration-specific incidence was stable throughout the study period (P=0.8). The age-sex-adjusted incidence of ESRD increased between 1967 and 1990 and declined thereafter. The incidence of proteinuria increased over 36 years in Pima Indians as the proportion of people with diabetes of long duration increased. On the other hand, the incidence of ESRD declined after 1990, coinciding with improved control of blood pressure, hyperglycemia, and perhaps other risk factors.