Changes in proteinuria and the associated risks of ischemic heart disease, acute myocardial infarction, and angina pectoris in Korean population

Sung Keun Park(Sung Keun Park),Ju Young Jung(Ju Young Jung),Min-Ho Kim(Min-Ho Kim),Chang-Mo Oh(Chang-Mo Oh),Eunhee Ha(Eunhee Ha),Eun Hye Yang(Eun Hye Yang),Hyo Choon Lee(Hyo Choon Lee),Soonsu Shin(Soo 한국역학회 2023 Epidemiology and Health Vol.45 No.-

OBJECTIVES: Proteinuria is widely used to predict cardiovascular risk. However, there is insufficient evidence to predict how changes in proteinuria may affect the incidence of cardiovascular disease. METHODS: The study included 265,236 Korean adults who underwent health checkups in 2003-2004 and 2007-2008. They were categorized into 4 groups based on changes in proteinuria (negative: negative → negative; resolved: proteinuria ≥1+ → negative; incident: negative → proteinuria ≥1+; persistent: proteinuria ≥1+ → proteinuria ≥1+). We conducted 6 years of follow-up to identify the risks of developing ischemic heart disease (IHD), acute myocardial infarction (AMI), and angina pectoris according to changes in proteinuria. A multivariate Cox proportional-hazards model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident IHD, AMI, and angina pectoris. RESULTS: The IHD risk (expressed as HR [95% CI]) was the highest for persistent proteinuria, followed in descending order by incident and resolved proteinuria, compared with negative proteinuria (negative: reference, resolved: 1.211 [95% CI, 1.104 to 1.329], incident: 1.288 [95% CI, 1.184 to 1.400], and persistent: 1.578 [95% CI, 1.324 to 1.881]). The same pattern was associated with AMI (negative: reference, resolved: 1.401 [95% CI, 1.048 to 1.872], incident: 1.606 [95% CI, 1.268 to 2.035], and persistent: 2.069 [95% CI, 1.281 to 3.342]) and angina pectoris (negative: reference, resolved: 1.184 [95% CI, 1.065 to 1.316], incident: 1.275 [95% CI, 1.160 to 1.401], and persistent: 1.554 [95% CI, 1.272 to 1.899]). CONCLUSIONS: Experiencing proteinuria increased the risks of IHD, AMI, and angina pectoris even after proteinuria resolved.

학교 신체 검사에서 발견된 단독 단백뇨의 분석

오동환,김정수,박지경,정우영,Oh Dong-Hwan,Kim Jung-Soo,Park Ji-Kyoung,Chung Woo-Yeong 대한소아신장학회 2003 Childhood kidney diseases Vol.7 No.2

목적 : 초, 중, 고등학생들을 대상으로 실시한 집단뇨 검사의 전반적인 분석에 대한 연구 결과들은 여러 연구자들에 의해 지속적으로 보고되었으나, 단독 단백뇨(isolated proteinuria)에 대한 연구는 소수에 불과하다. 국내에서는 매년 전체학생의 0.3-0.5% 정도를 차지하는 것으로 보고되어 있다. 단백뇨는 과도한 양의 단백이 소변으로 배출되는 것으로, 증상이 없는 환자에서 발견된 단백뇨는 심각한 신장질환이나 전신 질환의 초기 발현이거나 혹은 임상적으로 의미 없는 일시적인 소견일 수 있다. 그러나 지속적인 단백뇨의 경우는 향후 진행성 신질환의 경과를 취하는 경우가 적지 않으므로 진단 당시 정확한 검사 및 지속적인 외래 추적 관찰이 필수적이다. 이에 저자들은 부산 경남지방에 거주하는 초, 중, 고등학교 학생들 중학교 신체검사에서 우연히 발견된 단독 단백뇨를 주소로 본 원을 방문하였던 학생들을 대상으로, 단독 단백뇨의 원인을 규명하고, 전국적인 자료 구축의 기본적인 데이터를 제공하고자 본 연구를 시행하였다. 방법 : 2002년 4월부터 2003년 8월까지 학교 신체 검사에서 발견된 소변 검사상의 이상 소견을 주소로 부산백병원 소아과를 방문하였던 학생 중 단독 단백뇨의 소견을 보였던 초, 중, 고등학생 44명을 대상으로 전향적으로 조사하였다. 성별은 남자가 15명, 여자가 29명으로 남녀 비는 1:1.93이었다. 연령은 7세부터 16.9세까지로 평균 연령은 12.0세였다. 모든 학생들은 소아신장학회의 프로토콜에 의거하여 검사를 시행하였다. 결과 : 단독 단백뇨를 보였던 44명 학생들에서 단백뇨의 원인적 분석 결과는 일시적 단백뇨가 4례(9.1%), 기립성 단백뇨가 36례(81.8%), 지속성 단백뇨가 4례(9.1%)로, 기립성 단백뇨가 가장 많았다. 본원에 의뢰된 학생들의 학교 신체검사상에서의 단백뇨 정성검사(urine dipstick test) 결과를 보면, 전체적으로 2+가 24례(54.5%)로 가장 많았으며, Trace와 3+가 각각 6례, 1+ 5례, 4+ 3례였다. 기립성 단백뇨 군에서는 2+가 21례(58.3%)로 가장 많았다. 24시간 채집뇨상의 총단백량은 일시적 단백뇨 군에서는 평균 $121.0{\pm}136.4\;mg$이었고, 기립성 단백뇨 군은 평균 $179.1{\pm}130.0\;mg$, 지속성 단백뇨 군은 $1,532.8{\pm}982.5\;mg$이었다. 기립성 단백뇨 군에서는 24시간 채집뇨상의 총단백량의 범위가 40 mg에서 616 mg까지로 비교적 넓은 범위를 나타내었다. 단회뇨를 이용하여 측정한 PCR은 일시적 단백뇨군에서는 평균 $0.10{\pm}0.01$이었고, 기립성 단백뇨군은 평균 $0.61{\pm}0.61$, 지속성 단백뇨 군은 평균 $4.35{\pm}4.04$이었다. 기립성 단백뇨 군에서는 PCR의 범위가 0.09에서 2.32까지의 편차를 나타내었다. 지속성 단백뇨를 보이는 경우가 4례에서 관찰되었다. 이들 모두는 1년 동안 계속하여 단백뇨가 나타났으며, 결국 신조직 검사를 시행하였다. 1례는 미세병변이었고, 나머지 2례는 막증식성 사구체 신염이였으며, 나머지 1례는 신유전분증이었다. 결론 : 단백뇨의 검출은 신장질환의 존재를 확인해 줄 뿐만이 아니라 지속적인 단백뇨는 진행성 경과의 위험성을 동시에 암시해 주는 매우 유용한 지표이다. 본 연구 결과 학교 신체 검사상에서 발견된 단독 단백뇨의 주된 원인은 기립성 단백뇨로 81.8%를 차지하였다. 그러나 지속성 단백뇨의 경우 비록 9.1%의 빈도를 보였지만, 신장 조직검사를 시행한 결과 진행성 경과를 취할 수 있는 막 증식성 사구체 신염과 매우 Purpose : The urinary mass screening program for the detection of urinary abnormalities in school aged population has been performed in Seoul since 1981. Nation-wide urinary mass screening program was also performed since 1998. The aim of this study was to analyze the cause and nature of isolated proteinuria detected by chance on the urinary mass screening test in Busan and Kyungsangnam-do Province Methods : The medical records of 44 cases of isolated proteinuria detected by chance on the urinary mass screening test in Busan and Kyungsangnam-do Province, and evaluated for urinary abnormalities at the pediatrics outpatients renal clinics of Busan Paik Hospital from April 2002 to August 2003 were reviewed prospectively. Results : The cause and incidence of isolated proteinuria were as follows; transient proteinuria 4 cases(9.1%), orthostatic proteinuria 36 cases(81.8%) and persistent proteinuria 4 cases (9.1%). The total protein amount of the 24 hour urine were $121.0{\pm}136.4\;mg$ in transient proteinuria, $179.1{\pm}130.0\;mg$ in orthostatic proteinuria and $1532.8{\pm}982.5\;mg$ in persistent proteinuria. In the orthostatic proteinuria group, the total protein amount of the 24 hour urine was in the range of 40-616 mg. Spot urine protein/creatinine ratio(PCR) were $0.10{\pm}0.01$ in transient proteinuria, $0.61{\pm}0.61$ in orthostatic proteinuria and $4.35{\pm}4.04$ in persistent proteinuria. In the orthostatic proteinuria group, spot me PCR was in the range of 0.09-2.32. Renal biopsy was peformed in 4 children of the persisitent proteinuria group. They showed minimal change in 1 case, membranoproliferatiye glomerulonephritis in 2 cases and secondary renal amyloidosis in 1 case. Conclusion : The majority of isolated proteinuria which was detected by chance on school urinary mass screening were transient or orthostatic proteinuria. Even though the incidence of persistent proteinuria was much lower, it is necessary to take care of these children regularly and continuously, because persistent proteinuria itself is a useful marker of the progressive renal problems.

학동기 아동의 무증상 단백뇨에 대한 분석

이종국 인제대학교 1988 仁濟醫學 Vol.9 No.4

1987년도 초ㆍ중ㆍ고학생들을 대상으로 시행된 학생 집단 뇨검사에서 양성으로 확인된 학생들에게 정밀검사를 실시한 결과 2차에 걸쳐 양성을 보인 학생들 중 34% 정도가 신질환과 관계 있을 수 있는 무증상 단백뇨증을 가지고 있었다. 단백뇨와 혈뇨를 동시에 가지고 있는 학생들 중 8명에 시행한 병리조직학적 검사에서는 6명에서 심각한 신질환을 확인할 수 있었다. Mass screening program for the detection of proteinuria and glycosuria had been performed for a school-age population in the city of Seoul since 1981. Annually, about a half million students in Seoul, which comprised of three different grades -the 5th in elementary schools, the 2nd in middle schools and the 2nd in high schools, corresponding to the average ages of 11, 14 and 17 years, respectively- had been subjected to be a population for the program. Even though proteinuria used to be found in 0.25-0.45% of a population sampled annually, clinical evaluations have not be done so far. A clinical evaluation, therefore, was designed for schoolchildren with proteinuria in the initial screening in 1987 to determine the prevalence rates of asymptomatic proteinuria in a school-age population and the risk of underlying renal disease as well as to obtain guideline for further clinical evaluation. The initial screening for proteinuria was done by testing urine specimens obtained at convenient times at schools during annual physical checkups. Those students with proteinuria positive in the initial screening test underwent the second test at the school health center. Those who showed proteinuria in the second test were referred to the author and were put on the clinical evaluation. Of 557,048 students who participated in the initial mass screening, 2,024 (0.36%) were noted to have proteinuria. The prevalence rate of asymptomatic proteinuria was high among 14 age-group compaired to others. Considering the difference by sex, it was high in girls in 11 age-group but in boys in 17 age-group. A total of 841 (41%) among 2,024 complied the 2nd test. Of them, 463 (55%) showed proteinuria. A total of 149 students were referred to for the clinical evaluation. The distribution by the pattern of proteinuria was the following : transient proteinuria 10 (6.7%), orthostatic proteinuria 88 (59,1%), constant proteinuria 18 (12.1%), proteinuria & hematuria 30 (20.1%), transient proteinuria & hematuria 3 (2.0%). Laboratory examinations were not helpful to exclude serious renal diseases. Renal pathologic examinations performed on 8 children with proteinuria and hematuria revealed 4 IgA Nephropathy, 1 HBV-associated Membranous Nephropathy, 1 MPGN and 2 mild Focal Nonspecific Glomerulonephritis.

Clinicopathological features of diabetic and nondiabetic renal diseases in type 2 diabetic patients with nephrotic-range proteinuria

Lee, Yu Ho,Kim, Ki-Pyo,Kim, Yang Gyun,Moon, Ju-Young,Jung, Su Woong,Park, Eunji,Kim, Jin Sug,Jeong, Kyung-Hwan,Lee, Tae Won,Ihm, Chun-Gyoo,Jo, Young-Il,Choi, Hoon-Young,Park, Hyeong-Cheon,Lee, So-Youn Williams & Wilkins Co 2017 Medicine Vol.96 No.36

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>Heavy proteinuria with or without features of nephrotic syndrome is associated with many primary and systemic diseases. For diabetic patients, distinguishing nondiabetic renal disease (NDRD) from diabetic nephropathy (DN) is important in choosing treatment modalities and determining renal prognosis. However, clinical relevance of heavy proteinuria is inconsistent with clinical DN assessments. This study investigated the clinicopathological features and renal outcomes of DN and NDRD in type 2 diabetic patients with nephrotic-range proteinuria.</P><P>We enrolled 220 cases of type 2 diabetic patients who underwent renal biopsy. They were grouped according to the presence of nephritic-range proteinuria and pathological features. Baseline characteristics, laboratory findings, types of pathological diagnosis, and renal outcomes were analyzed in patients with heavy proteinuria.</P><P>Upon kidney biopsy, 129 patients (58.6%) showed nephritic-range proteinuria. Patients with heavy proteinuria (an average urine protein-to-creatinine ratio of 10,008 ± 7307 mg/gCr) showed lower serum albumin levels and higher total cholesterol levels, but did not show any difference in age, duration of diabetes, renal function, or the presence of retinopathy compared with those with mild-to-moderate proteinuria (an average urine protein-to-creatinine ratio of 1581 ± 979 mg/gCr). Renal biopsy revealed that the prevalence of NDRD was 37.2% in patients with heavy proteinuria, which was significantly lower than that in patients with mild-to-moderate proteinuria (63.7%). The most common pathological types of NDRD were membranous nephropathy (41.7%), IgA nephropathy (14.6%), and minimal change disease (10.4%). NDRD patients showed lower prevalence of diabetic retinopathy and better kidney function irrespective of proteinuria. Immunosuppressive treatment was administered more frequently in patients with heavy proteinuria (56.3%) compared with patients with mild-to-moderate proteinuria (20%) because of the pathological differences according to the amount of proteinuria. Renal outcomes were significantly worse in patients with DN than in patients with NDRD.</P><P>DN patients with heavy proteinuria exhibited different prevalence of NDRD and worse prognosis. Renal biopsy in type 2 diabetic patients should be more extensively considered to accurately diagnose NDRD, guide further management, and predict renal outcomes, especially in patients with nephrotic-range proteinuria.</P></▼2>

Determination of the optimal target level of proteinuria in the management of patients with glomerular diseases by using different definitions of proteinuria

Kee, Youn Kyung,Yoon, Chan-Yun,Kim, Seung Jun,Moon, Sung Jin,Kim, Chan Ho,Park, Jung Tak,Lim, Beom Jin,Chang, Tae Ik,Kang, Ea Wha,Kie, Jeong Hae,Yoo, Tae-Hyun,Jeong, Hyun Joo,Kang, Shin-Wook,Han, Seun Williams & Wilkins Co 2017 Medicine Vol.96 No.44

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>Proteinuria is a major determinant of adverse renal outcome, and its reduction slows renal progression in glomerular diseases. However, the optimal target of proteinuria in glomerular diseases is unclear, and discrepancies in the definition of proteinuria produce ambiguous findings. Here we investigated the optimal target of proteinuria by using different definitions of proteinuria. We analyzed 574 IgA nephropathy (IgAN), 175 membranous nephropathy (MGN), and 177 focal segmental glomerulosclerosis (FSGS) cases from 3 Korean kidney centers. We evaluated the impact of proteinuria on renal outcome with 2 definitions: time-average proteinuria (TAP) and time-varying proteinuria (TVP). The endpoint was renal progression, defined as a 50% decline in glomerular filtration rate or end-stage renal disease. During a median follow-up of 57.3 months, the primary outcome occurred in 54 patients with IgAN, 26 with MGN, and 30 with FSGS. Multivariate Cox regression using TAP indicated that there was a linear association between proteinuria and risk of renal progression in IgAN. However, moderate proteinuria was not associated with an increased risk of renal progression in MGN and FSGS. In contrast, the analysis by TVP showed that the risk significantly increased in proportion to proteinuria during follow-up in all 3 diseases. Our findings suggest that TVP-based model can delineate association between proteinuria and risk of renal progression better than TAP-based model, considering that TVP reflects the dynamic change of proteinuria over time. Thus, proteinuria reduction to the lowest possible level is required to improve renal outcomes in patients with glomerular diseases.</P></▼2>

소아 연구균 감염후 급성 사구체신염에서 단백뇨의 발생과 그 예후

정우철,이효성,신윤혜,배기수,Jeoung, Woo-Chul,Lee, Hyo-Sung,Shin, Yun-Hye,Pai, Ki-Soo 대한소아신장학회 2006 Childhood kidney diseases Vol.10 No.2

Purpose : The prognosis of acute poststreptococcal glomerulonephritis(APSGN) has been reported to be favorable. However, several studies have reported that patients with nephrotic range proteinuria in the acute phase or persistent proteinuria may progress to chronic renal failure. To elucidate this further, we analyzed the features of proteinuria and its prognosis in pediatric patients with APSGN. Methods : A total of 48 children with APSGN admitted to our hospital between Jan. 2000 and Dec. 2004 were included. After discharge from the hospital, patients were regularly followed up every month by clinical evaluations and laboratory tests including routine urinalysis and quantification of proteinuria. Results : Age of the patients ranged from 3 to 15 years(median 5.8 years) at the time of disease onset. Proteinuria was present in 34(70.8%) patients and 5 of them showed heavy proteinuria. Proteinuria normalized within one month in most patients(82.3%) and there was no one with proteinuria after 6 months. Cyclosporine A(5 mg/kg/day in two divided doses) was given to 3 patients with massive proteinuria that lasted longer than 2 months and the result was complete remission within 4 months. Conclusions : Our data indicated that the prognosis of APSGN during childhood is excellent. Children with severe proteinuria or subnormal renal function in poststreptococcal glomerulonephritis had favorable prognosis without chronic renal failure, and children with crescentic formation also had favorable prognosis. Three patients who continued to have heavy proteinuria for more than 2 months received cyclosporine A and remission of proteinuria was achieved within a couple of months.

Association Between High Platelet Indices and Proteinuria in Patients With Hypertension

Ihsan Ates,Mesudiye Bulut,Nihal Ozkayar,Fatih Dede 대한진단검사의학회 2015 Annals of Laboratory Medicine Vol.35 No.6

Background: We aimed to determine the association between platelet indices including plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), and proteinuria associated with hypertension (HT) as well as the relative power of each to predict proteinuria. Methods: The study included 223 patients (68 men and 155 women) with primary HT. PCT, MPV, PDW, and proteinuria levels were measured. The patients were divided into two groups according to proteinuria status based on 24-hr urinary protein excretion: proteinuria (+) group (15 men and 40 women) and proteinuria (-) group (53 men and 115 women). Results: The mean and SD of platelet count, PDW, PCT, and MPV were 278.8±49.6 ×109/L, 13.5±1.8%, 0.31±0.07%, and 11.3±2.6 fL, respectively. The mean platelet count, PCT, MPV, and PDW were significantly higher in the proteinuria (+) group than in the proteinuria (-) group (P<0.05); there were no significant differences in the other blood parameters between the two groups. The platelet count, PCT, MPV, and PDW were independent risk factors predictive of proteinuria according to a stepwise regression analysis of PDW, PCT, and MPV. PCT was the strongest independent predictor of proteinuria. Conclusions: The platelet indices PCT, PDW, and MPV were significantly higher in patients with proteinuria than in those without it. Among these three indices, PCT was the strongest predictor of proteinuria.

Proteinuria as a Risk Factor for Mortality in Patients with Colorectal Cancer

김민지,강용운,김창성,최준석,배은휘,마성권,권순석,김수완 연세대학교의과대학 2013 Yonsei medical journal Vol.54 No.5

Purpose: We investigated the effects of proteinuria and renal insufficiency on all-cause mortality in patients with colorectal cancer, with special emphasis on cancer staging and cancer-related deaths. Materials and Methods: We retrospectively studied a cohort of patients with colorectal cancer. In protocol 1, patients were classified into four groups based on the operability of cancer and proteinuria: group 1, early-stage cancer patients (colorectal cancer stage ≤3) without proteinuria;group 2, early-stage cancer patients with proteinuria; group 3, advanced-stage cancer patients without proteinuria (colorectal cancer stage=4); and group 4, advanced-stage cancer patients with proteinuria. In protocol 2, patients were classified into four similar groups based on cancer staging and renal insufficiency (eGFR <60 mL/min/1.73 m2). Between January 1, 1998 and December 31, 2009, 3379 patients were enrolled in this cohort and followed until May 1, 2012 or until death. Results: The number of patients with proteinuria was 495 (14.6%). The prevalence of proteinuria was higher in advanced-stage cancer (n=151, 22.3%) than in early-stage cancer patients (n=344, 12.7%). After adjusting for age, gender and other clinical variables, the proteinuric, early-stage cancer group was shown to be associated with an adjusted hazard ratio of 1.67 and a 95% confidence interval of 1.38-2.01, compared with non-proteinuric early-stage cancer patients. However, renal insufficiency was not associated with colorectal cancer mortality. Conclusion:Proteinuria is an important risk factor for cancer mortality, especially in relatively early colorectal cancer.

Clinical Approach to Children with Proteinuria

장경미,조민현 대한소아신장학회 2017 Childhood kidney diseases Vol.21 No.2

Proteinuria is common in pediatric and adolescent patients. Proteinuria is defined as urinary protein excretion at levels higher than 100-150 mg/m2/day in children. It can be indicative of normal or benign conditions as well as numerous types of severe underlying renal or systemic disease. The school urine screening program has been conducted in Korea since 1998. Since then, numerous patients with normal or benign proteinuria as well as early stage renal diseases have been referred to the hospital. Benign proteinuria includes orthostatic proteinuria and transient proteinuria. Most causes of proteinuria can be categorized into 3 types: 1) overflow, 2) tubular, and 3) glomerular. Although treatment should be directed at the underlying cause of the proteinuria, prompt evaluation, diagnosis, and long-term monitoring of these pediatric patients can prevent potential progression of the underlying disease process. This article provides an overview of proteinuria: its causes, methods of assessment, and algorithmic suggestions to differentiate benign from pathologic renal disease.

Clinical Approach to Children with Proteinuria

Jang, Kyung Mi,Cho, Min Hyun Korean Society of Pediatric Nephrology 2017 Childhood kidney diseases Vol.21 No.2

Proteinuria is common in pediatric and adolescent patients. Proteinuria is defined as urinary protein excretion at levels higher than $100-150mg/m^2/day$ in children. It can be indicative of normal or benign conditions as well as numerous types of severe underlying renal or systemic disease. The school urine screening program has been conducted in Korea since 1998. Since then, numerous patients with normal or benign proteinuria as well as early stage renal diseases have been referred to the hospital. Benign proteinuria includes orthostatic proteinuria and transient proteinuria. Most causes of proteinuria can be categorized into 3 types: 1) overflow, 2) tubular, and 3) glomerular. Although treatment should be directed at the underlying cause of the proteinuria, prompt evaluation, diagnosis, and long-term monitoring of these pediatric patients can prevent potential progression of the underlying disease process. This article provides an overview of proteinuria: its causes, methods of assessment, and algorithmic suggestions to differentiate benign from pathologic renal disease.