Determinants of non-diabetic kidney diseases in type 2 diabetic patients: Twenty years of single center experience.

BACKGROUND: Diabetic nephropathy is one of the most common complications associated with diabetes. However, non-diabetic kidney disease has been reported in patients with type 2 diabetes at varying incidence rates. The objective of our study is to investigate the occurrence, clinicopathological characteristics, and inflammatory markers linked to diabetic and non-diabetic nephropathy (NDN) in patients with type 2 diabetes mellitus (DM). Additionally, we aimed to explore the possibility of identifying non-diabetic pathology using different biopsy indications. MATERIALS AND METHODS: A total of 159 patients with type 2 DM who underwent renal biopsy at a tertiary care nephrology clinic between January 2000 and January 2022 were enrolled in the study. We collected comprehensive data, including patient demographics, co-morbidities, diabetes duration, renal biopsy indications and results, serological markers, renal function, diabetic retinopathy (DRP), full blood count, blood biochemistry, urinalysis, and inflammatory markers. Patients were categorized based on their biopsy indications, and their biopsy results were classified into three groups: isolated NDN, isolated diabetic nephropathy (DN), and mixed nephropathy with concurrent NDN. We evaluated the relationship between biopsy indications and accompanying pathologies and statistically assessed the likelihood of each biopsy indication detecting non-diabetic renal pathology. Additionally, differences in other data, including demographic and laboratory results and medical histories, among the three groups were investigated. RESULTS: The most frequent indication of renal biopsy was atypical presentations of nephrotic syndrome or nephrotic range proteinuria (ANS/ANP) in 25.1% of patients. Other indications included unexplained renal failure (URF) in 22.6%, atypical presentations of non-nephrotic range proteinuria (ANNP) in 18.2%, acute kidney injury or rapidly progressive kidney dysfunction (AKI/RPKD) in 16.9%, microscopic hematuria in 15.7%, URF with ANNP in 11.3%, and severe nephrotic range proteinuria (SNP) in 9.4%. Renal biopsy revealed isolated NDN in 64.8%, DN in 25.1%, and mixed nephropathy in 10.1% of patients. Primary glomerular diseases were the main non-diabetic renal pathology, predominantly focal segmental glomerulosclerosis (FSGS) (36.4%) followed by MN (10.6%) and IgA nephropathy (7.5%). In comparison with the isolated DN and mixed nephropathy groups, patients in the isolated NDN group had significantly shorter diabetes duration, fewer DRP, as well as lower serum creatinine and neutrophil-to-lymphocyte ratio (NLR). Multivariate logistic regression analysis revealed that presence of hematuria (OR 4.40; 95% CI 1.34 - 14.46, p = 0.014), acute nephrotic range proteinuria (OR 11.93; 95% CI 1.56 - 90.77, p = 0.017), and AKI/APKD (OR 41.08; 95% CI 3.40 - 495.39, p = 0.003) were strong predictors of NDN. Lower NLR (OR 0.77; 95% CI 0.60 - 0.98, p = 0.035), shorter duration of diabetes (OR 0.90; 95% CI 0.84 - 0.97, p = 0.010), and absence of DRP (OR 0.35; 95% CI 0.12 - 0.98, p = 0.046) were also found to be independent indicators of NDN. Receiver operating characteristic curve (ROC) analysis revealed a cut-off value of ≤ 3.01 for NLR (sensitivity of 63.1%, specificity of 63.5%) with regards to predicting non-diabetic renal pathology (p = 0.006). CONCLUSION: Renal biopsy findings in patients with type 2 DM highlight that the prevalence of NDN may be higher than assumed, as presented mainly in the form of primary glomerular disease. The presence of AKI/RPKD, hematuria, and ANS/ANP serves as a reliable indicator of non-diabetic renal pathology. In more ambiguous situations, factors such as a shorter duration of diabetes, absence of DRP, and a lower NLR value may assist clinicians in biopsy decision.

Admission proteinuria predicts the incidence of acute kidney injury among patients with acute ST-segment elevation myocardial infarction: a retrospective cohort study.

BACKGROUND: Proteinuria indicates renal dysfunction and is associated with the development of acute kidney injury (AKI) in several conditions, but the association between proteinuria and AKI in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. This research aims to investigate the predictive value of proteinuria for the development of AKI in STEMI patients. METHODS: A total of 2735 STEMI patients were enrolled. The present study's endpoint was AKI incidence during hospitalization. AKI is defined according to the Kidney Disease: Improving Global Outcomes criteria. We defined proteinuria, measured with a dipstick, as mild (1+) or heavy (2+ to 4+). Multivariate logistic regression and subgroup analyses were used to testify to the association between proteinuria and AKI. RESULTS: Overall, proteinuria was observed in 634 (23.2%) patients. Multivariate logistic regression analyses revealed that proteinuria [odds ratio (OR), 1.58; 95% confidence interval (CI), 1.25-2.00; P  < 0.001] was the independent predictive factor for AKI. Severe proteinuria was associated with a higher adjusted risk for AKI compared with the nonproteinuria group (mild proteinuria: OR, 1.35; 95% CI, 1.04-1.75; P  = 0.025; severe proteinuria: OR, 2.50; 95% CI, 1.70-3.68; P  < 0.001). The association was highly consistent across all studied subgroups. (all P for interaction >0.05). CONCLUSION: Admission proteinuria measured using a urine dipstick is an independent risk factor for the development of AKI in STEMI patients.

Population characteristics and diagnosis rate of chronic kidney disease by eGFR and proteinuria in Japanese clinical practice: an observational database study.

Chronic kidney disease (CKD) guidelines recommend early identification and intervention to delay the progression of CKD. The Kidney Disease: Improving Global Outcomes (KDIGO) heatmap is widely used for risk evaluation in CKD management; however, real-world evidence on clinical characteristics based on the KDIGO heatmap remains limited worldwide including Japan. In order to understand the management of CKD including its diagnostic rates in a Japanese clinical setting on the basis of KDIGO heatmap, we utilized a medical record database that contains estimated glomerular filtration rate (eGFR) and urine protein data. Adult individuals (≥ 18 years) with two eGFR results of < 90 mL/min/1.73 m2, 90-360 days apart, were included. Approximately half of patients (452,996/788,059) had proteinuria test results and 6.9% (54,073) had quantitative results. CKD diagnosis rate in patients without proteinuria data was 5.9%, with a lower rate (2.9%) in stage G2; the corresponding rates with quantitative test results were 43.5% and 31.3%, respectively. The most frequent comorbidities were hypertension, diabetes, and cardiovascular disease, and their prevalence increased as the eGFR and proteinuria stages progressed. This study revealed a low rate of proteinuria assessment, especially using quantitative methods, and diagnosis in individuals with suspected CKD. With emerging treatment options to prevent CKD progression and complication onset, there is a need for early evaluation and diagnosis of CKD.

Proteinuria among Pregnant Women Admitted to the Department of Obstetrics and Gynaecology of a Tertiary Care Centre.

Introduction: Proteinuria is usually related with preeclampsia during pregnancy, although it can also be caused by other conditions such as renal disease or isolated proteinuria. Proteinuria during pregnancy can result in adverse fetomaternal outcomes. The study aimed to find the prevalence of proteinuria among pregnant women admitted to the Department of Obstetrics and Gynaecology of a tertiary care centre. Methods: A descriptive cross-sectional study was carried out among pregnant women in the Department of Obstetrics and Gynaecology after obtaining ethical approval from the Institutional Review Committee. Data of 14 April 2022 to 13 April 2023 was collected from 9 June 2023 to 9 September 2023 from medical records. The study included pregnant women aged 18-45 years, who were past 28 weeks of gestation and had a 24-hour urine protein measurement. Pregnant women who had insufficient medical records were excluded from the study. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 3,914 pregnant women, proteinuria was seen in 61 (1.56%) (1.17-1.95, 95% Confidence Interval). The mean proteinuria in the study group was 1.5±2.75 gm/24 hr. In pregnant women with proteinuria, maternal complications were seen in 51 (83.60%) and foetal complications in 34 (55.73%) cases. A total of 47 (77.05%) underwent emergency lower-section caesarean section. Conclusions: The prevalence of proteinuria among pregnant women was found to be similar as compared to studies done in similar settings. Keywords: preeclampsia; pregnancy complications; proteinuria.

Prevalence of proteinuria and its associated factors in hypertensive diabetic patients.

OBJECTIVE: Hypertensive diabetic patients are at increased risk for chronic kidney disease. Proteinuria is an early sign of kidney damage. Limited research is available on proteinuria and on its associated factors in hypertensive patients with diabetes. This study aimed to assess the prevalence of proteinuria and its associated factors in hypertensive diabetic patients. PATIENTS AND METHODS: The current retrospective study utilized medical records and hospital computers to collect sociodemographic and medical information about the study patients in two major hospitals in Jordan. Binary regression analysis was used to find the factors that are significantly and independently associated with the presence of proteinuria. RESULTS: Data from 522 hypertensive diabetic patients were investigated. Factors including age (OR=0.691; 95% CI: 0.930-0.994; p<0.01), high-density lipoprotein level (OR=0.450; 95% CI: 0.211-0.960; p<0.05), and higher glomerular filtration rate (OR=0.964; 95% CI: 0.950-0.977; p<0.01) were associated with proteinuria among the study patients. In contrast to metformin (OR=0.237; 95% CI: 0.098-0.572; p<0.01), patients who received insulin (OR=1.992; 95% CI: 1.136-3.492; p<0.05), thiazide diuretics (OR=1.848; 95% CI: 1.108-3.083; p<0.05), calcium channel blockers (OR=1.833, 95% CI: 1.110-3.028, p<0.05), or beta-blockers (BBs) (OR=2.199, 95% CI: 1.257-3.848, p<0.01) had a higher likelihood of having proteinuria. CONCLUSIONS: For preserving kidney function, it is deemed necessary to perform regular checkups for proteinuria among hypertensive diabetic patients, particularly in young patients, patients with low levels of high-density lipoprotein, and those with a lower glomerular filtration rate.

Determinants of poor glycaemic control and proteinuria in patients with type 2 diabetes: a retrospective analysis of general practice records in Ireland.

BACKGROUND: Analysis of general practice records can address the information gap on the epidemiology of type 2 diabetes (T2DM) in Ireland, informing practice and the development of interventions in primary care. The aim of this study was to identify patients with poor glycaemic control, risk factors for complications and evidence of end organ damage in a large multi-practice study and to profile their characteristics. METHODS: Patients with T2DM were identified using disease coding in Health One practice management software in 41 general practices. Patients' demographics and clinical data were extracted. Rates of poor glycaemic control (glycated haemoglobin > 58 mmol/mol) and albumin creatinine ratio > 3 mg/mmol were calculated. A multilevel logistic regression analysis using both patient and practice variables was conducted. RESULTS: Data was collected from 3188 patients of whom 29% (95% CI 28 to 31%) had poor glycaemic control, which was associated with younger age, higher BMI and higher total cholesterol. Only 42% of patients (n = 1332) had albumin creatinine ratio measured with 42% (95% CI 40 to 45%) of these having values > 3 mg/mmol. Older age groups, men, those with hypertension, eGFR < 60 ml/min/1.73m2 and poor glycaemic control were most associated with higher values of albumin creatinine ratio. CONCLUSIONS: Analysing this large multi-practice dataset gives important information on the prevalence and characteristics of diabetic patients who are most at risk of poor outcomes. It highlights that recording of some data could be improved.

Early-Stage Chronic Kidney Disease and Related Health Care Spending.

Importance: The global burden of chronic kidney disease (CKD) is substantial and potentially leads to higher health care resource use. Objective: To examine the association between early-stage CKD and health care spending and its changes over time in the general population. Design, Setting, and Participants: Cohort study using nationwide health checkup and medical claims data in Japan. Participants included individuals aged 30 to 70 years with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m2 or greater at the baseline screening in 2014. Data analyses were conducted from April 2021 to October 2023. Exposure: The CKD stages at baseline, defined by the eGFR and proteinuria, were as follows: eGFR of 60 mL/min/1.73 m2 or greater without proteinuria, eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. Main Outcome and Measures: The primary outcome was excess health care spending, defined as the absolute difference in health care spending according to the baseline CKD stages (reference group: eGFR ≥60 mL/min/1.73 m2 without proteinuria) in the baseline year (2014) and in the following 5 years (2015 to 2019). Results: Of the 79 988 participants who underwent a health checkup (mean [SD] age, 47.0 [9.4] years; 22 027 [27.5%] female), 2899 (3.6%) had an eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, 1116 (1.4%) had an eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and 253 (0.3%) had an eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. At baseline, the presence of proteinuria and an eGFR less than 60 mL/min/1.73 m2 were associated with greater excess health care spending (adjusted difference, $178; 99% CI, $6-$350 for proteinuria; $608; 99% CI, $233-$983 for an eGFR of 30-59 mL/min/1.73 m2; and $1254; 99% CI, $134-$2373 for their combination). The study consistently found excess health care spending over the following 5 examined years. Conclusions and Relevance: In this cohort study of nationwide health checkup and medical claims data in Japan, early-stage CKD was associated with excess health care spending over the 5 examined years, and the association was more pronounced with a more advanced disease stage.

Renal Function Impairment in Children With Congenital Cytomegalovirus Infection: A Cross-sectional Study.

BACKGROUND: We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital cytomegalovirus infection (cCMV) and their association with cCMV disease, viruria and antiviral treatment. METHODS: This cross-sectional study was done using the Spanish Registry of Congenital Cytomegalovirus Infection. First-morning urine samples were collected from January 2016 to December 2018 from patients <5 years old enrolled in Spanish Registry of Congenital Cytomegalovirus Infection. Samples were excluded in case of fever or other signs or symptoms consistent with acute infection, bacteriuria or bacterial growth in urine culture. Urinary protein/creatinine and albumin/creatinine ratios, urinary beta-2-microglobulin levels, hematuria and CMV viruria were determined. A 0.4 cutoff in the urinary albumin/protein ratio was used to define tubular (<0.4) or glomerular (>0.4) proteinuria. Signs and symptoms of cCMV at birth, the use of antivirals and cCMV-associated sequelae at last available follow-up were obtained from Spanish Registry of Congenital Cytomegalovirus Infection. RESULTS: Seventy-seven patients (37 females, 48.1%; median [interquartile range] age: 14.0 [4.4-36.2] months) were included. Symptom-free elevated urinary protein/creatinine and albumin/creatinine ratios were observed in 37.5% and 41.9% of patients, respectively, with tubular proteinuria prevailing (88.3%) over glomerular proteinuria (11.6%). Proteinuria in the nephrotic range was not observed in any patients. In multivariate analysis, female gender was the only risk factor for tubular proteinuria (adjusted odds ratio = 3.339, 95% confidence interval: 1.086-10.268; P = 0.035). cCMV disease at birth, long-term sequelae, viruria or the use of antivirals were not associated with urinalysis findings. CONCLUSIONS: Mild nonsymptomatic tubular proteinuria affects approximately 40% of infants and toddlers with mostly symptomatic cCMV in the first 5 years of life.

Long-Term Renal Involvement in Association with Fontan Circulation.

Multiorgan dysfunction is a concern of Fontan patients. To clarify the pathophysiology of Fontan nephropathy, we characterize renal disease in the long-term observational study. Medical records of 128 consecutive Fontan patients [median age: 22 (range 15-37) years old] treated between 2009 and 2018 were reviewed to investigate the incidence of nephropathy and its association with other clinical variables. Thirty-seven patients (29%) showed proteinuria (n = 34) or < 90 mL/min/1.73 m2 of estimated glomerular filtration rate (eGFR) (n = 7), including 4 overlapping cases. Ninety-six patients (75%) had liver dysfunction (Forns index > 4.21). Patients with proteinuria received the Fontan procedure at an older age [78 (26-194) vs. 56 (8-292) months old, p = 0.02] and had a higher cardiac index [3.11 (1.49-6.35) vs. 2.71 (1.40-4.95) L/min/m2, p = 0.02], central venous pressure [12 (7-19) vs. 9 (5-19) mmHg, p < 0.001], and proportion with > 4.21 of Forns index (88% vs. 70%, p = 0.04) than those without proteinuria. The mean renal perfusion pressure was lower in patients with a reduced eGFR than those without it [55 (44-65) vs. 65 (45-102) mmHg, p = 0.03], but no other variables differed significantly. A multivariable analysis revealed that proteinuria was associated with an increased cardiac index (unit odds ratio 2.02, 95% confidence interval 1.12-3.65, p = 0.02). Seven patients with severe proteinuria had a lower oxygen saturation than those with no or mild proteinuria (p = 0.01, 0.03). Proteinuria or a decreased eGFR differentially occurred in approximately 30% of Fontan patients. Suboptimal Fontan circulation may contribute to the development of proteinuria and reduced eGFR.

Association of COVID-19 Versus COVID-19 Vaccination With Kidney Function and Disease Activity in Primary Glomerular Disease: A Report of the Cure Glomerulonephropathy Study.

RATIONALE & OBJECTIVE: Patients with glomerular disease (GN) may be at increased risk of severe COVID-19, yet concerns over vaccines causing disease relapse may lead to vaccine hesitancy. We examined the associations of COVID-19 with longitudinal kidney function and proteinuria and compared these with similar associations with COVID-19 vaccination. STUDY DESIGN: Observational cohort study from July 1, 2021, to January 1, 2023. SETTING & PARTICIPANTS: A prospective observational study network of 71 centers from North America and Europe (CureGN) with children and adults with primary minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy. EXPOSURE: COVID-19 and COVID-19 vaccination. OUTCOME: Repeated measure of estimated glomerular filtration rate (eGFR); recurrent time-to-event outcome of GN disease worsening as defined by doubling of the urinary protein-creatinine ratio (UPCR) to at least 1.5g/g or increase in dipstick urine protein by 2 ordinal levels to 3+(300mg/dL) or above. ANALYTICAL APPROACH: Interrupted time series analysis for eGFR. Prognostic matched sequential stratification recurrent event analysis for GN disease worsening. RESULTS: Among 2,055 participants, 722 (35%) reported COVID-19 infection; of these, 92 (13%) were hospitalized, and 3 died (<1%). The eGFR slope before COVID-19 infection was-1.40mL/min/1.73m2 (± 0.29 SD); within 6 months after COVID-19 infection, the eGFR slope was-4.26mL/min/1.73m2 (± 3.02 SD), which was not significantly different (P=0.34). COVID-19 was associated with increased risk of worsening GN disease activity (HR, 1.35 [95% CI, 1.01-1.80]). Vaccination was not associated with a change in eGFR (-1.34mL/min/1.73m2±0.15 SD vs-2.16mL/min/1.73m2±1.74 SD; P=0.6) or subsequent GN disease worsening (HR 1.02 [95% CI, 0.79-1.33]) in this cohort. LIMITATIONS: Infrequent or short follow-up. CONCLUSIONS: Among patients with primary GN, COVID-19 infection was severe for 1 in 8 cases and was associated with subsequent worsening of GN disease activity, as defined by proteinuria. By contrast, vaccination against COVID-19 was not associated with change in disease activity or kidney function decline. These results support COVID-19 vaccination for patients with GN. PLAIN-LANGUAGE SUMMARY: In this cohort study of 2,055 patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy, COVID-19 resulted in hospitalization or death for 1 in 8 cases and was associated with a 35% increase in risk for worsening proteinuria. By contrast, vaccination did not appear to adversely affect kidney function or proteinuria. Our data support vaccination for COVID-19 in patients with glomerular disease.

The prevalence and risk factors of kidney disease in first degree relatives of patients with ESRD treatment - single center study.

OBJECTIVE: To determine the prevalence and risk factors of kidney disease in first degree relatives of patients undergoing treatment for end-stage renal disease. METHODS: The prospective, cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, from May 1 to July 31, 2021, and comprised patients undergoing treatment for end-stage renal disease at the pre-transplant out-patients clinic, and their first degree relatives. Risk factors of chronic kidney disease, including age, gender, body mass index, hypertension, diabetes mellitus, and the causes of index cases were investigated alongside proteinuria, haematuria and estimated glomerular filtration rate. Diagnosis was made according to the criteria of the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative. The participants were divided chronic kidney disease group 1, and healthy group 2. The risk factors were compared between the groups. Data was analysed using SPSS 22. RESULTS: Of the 1,406 subjects assessed, 266(19%) were ESRD patients; 175(65.8%) males and 91(34.2%) females with mean age 34.04±11.19 years. 1,140(81%) first degree relatives of these 266 ESRD patient were assessed; 595(52.2%) males and 545(47.8%) females with mean age 36.78±13.76 years. Among the relatives, 146 (12.8%) had chronic kidney disease out of which 54 (4.7%) were already aware of their underlying disease. Older age, hypertension and diabetes mellitus were among the risk factors for chronic kidney disease (p<0.05), while gender was not significantly different between groups 1 and 2 (p>0.05). The relatives of index cases with underlying stone disease were at higher risk of haematuria 39(22.4%), whereas the relatives of index cases with chronic glomerulonephritis were at higher risk of proteinuria 67(28.03%) compared to index cases of other kinds (p<0.05). CONCLUSIONS: Screening in the high-risk population might help to identify early chronic kidney disease patients for making suitable interventions to prevent disease progression.

[Prevalence, age and gender features of chronic kidney disease in patients with diabetes mellitus].

AIM: To study the prevalence, age and gender characteristics of chronic kidney disease (CKD) in patients with diabetes mellitus (DM). MATERIALS AND METHODS: In a case-control study, clinical and laboratory data were analyzed in 683 patients with DM (4.6% of patients with type 1 DM and 95.4% with type 2 DM) and kidney damage. The indicators of anthropometry, hemodynamics and biochemistry were studied. The glomerular filtration rate (GFR) was calculated using the CKD-EPI formula. RESULTS: The proportion of middle-aged and elderly patients with CKD was the most numerous, amounting to 39 and 38%, respectively. At the same time, anemia was more common in young people, and hypercholesterolemia (35.0%), proteinuria (47.5%) and signs of renal failure (45.0%) - in middle-aged patients with CKD. 47.0% study participants had C1 and C2 categories of changes in renal function. Mean levels of systolic blood pressure (BP), the prevalence of proteinuria were statistically significantly higher in women. When evaluating the correlations, we found statistically significant relationships between the calculated GFR and the level of body mass index, systolic BP, venous blood glucose and Hb in the subgroup of men. Among females, a significant relationship between the calculated GFR value was revealed with indicators of systolic and diastolic BP, venous blood glucose and Hb concentration. CONCLUSION: Our data indicate the existence of differences in the prevalence of CKD and associated risk factors for the progression of renal failure, depending on gender differences and living conditions of patients. In urban residents, CKD was most often associated with arterial hypertension and renal failure, while overweight, obesity, and proteinuria were significantly more common in rural areas. The incidence of proteinuria and mean levels of systolic BP were significantly higher in females. Further study of the issue under discussion seems promising from the standpoint of a personalized approach and the search for a new preventive strategy to combat both end-stage renal failure and its complications.

Impact of proteinuria on long-term prognosis in patients with coronary artery disease.

BACKGROUND: This study aimed to investigate the association between proteinuria and long-term prognosis in patients with coronary artery disease. METHODS: This was a single-center observational study. A total of 1351 patients were identified who underwent percutaneous coronary intervention, and whose urine data were available. Patients were divided into two groups according to the presence (n = 245) or absence (n = 1106) of proteinuria. All-cause and cardiovascular deaths were primarily evaluated. RESULTS: The prevalence rates of hypertension and diabetes were significantly higher, and the baseline estimated glomerular filtration rate (eGFR) was lower in patients with proteinuria than in those without proteinuria. During the median follow-up of 4.1 years (interquartile range, 1.7-6.8 years), the occurrences of all-cause and cardiovascular deaths were significantly higher in patients with proteinuria. Multivariable Cox regression analysis indicated that the presence of proteinuria was a significant predictor of cardiovascular death as well as age, BMI, reduced eGFR, and left ventricular ejection fraction. When stratified into four groups based on eGFR category (eGFR <60 or ≥60 ml/min/1.73 m2) and absence or presence of proteinuria, the incidence rates of all-cause and cardiovascular deaths were highest in patients with proteinuria and eGFR less than 60 ml/min/1.73 m2. Furthermore, the incidence rates of all-cause and cardiovascular deaths were significantly higher in patients with proteinuria among both diabetic and nondiabetic patients. CONCLUSION: Proteinuria is associated with the long-term prognosis, and all-cause and cardiovascular deaths in patients with coronary artery disease, regardless of eGFR and the presence or absence of diabetes mellitus.

A study of adverse maternal-foetal outcomes in nephrotic syndrome combined with preeclampsia.

BACKGROUND: Although the majority of pregnancies with preeclampsia are characterised by elevated blood pressure, preeclampsia is often associated with nephrotic syndrome with similar symptoms such as high proteinuria and bilateral lower limb oedema. In this study, we compared the maternal-foetal outcomes of pregnant women with preeclampsia in a population with nephrotic syndrome and explored the factors that contribute to the corresponding outcomes and disease development. METHODS: A total of 90 pregnant women were included in this study, of whom 30 had nephrotic syndrome and were diagnosed with preeclampsia during pregnancy, and 60 had nephrotic syndrome alone. Descriptive statistical analyses of baseline data were performed to analyse the effect of combined preeclampsia on maternal and foetal pregnancy outcomes using unadjusted and adjusted logistic regression models. RESULTS: In this study, the baseline data of the two study populations demonstrated no differences except for the history of caesarean section and 24-h proteinuria results, which were significantly different (P < 0.05). The risk of preterm birth in the nephrotic syndrome with preeclampsia group was 8.25 (95% CI:3.041-22.084 P < 0.05); for a low birth weight, the risk was 6.00 (95% CI:2.302-15.638 P < 0.05); for foetal distress,the risk was 5.667 (95% CI:2.070-15.514 P < 0.05); and the risk of foetal birth restriction was 7.429 (95% CI: 2.642-20.885 P < 0.05). A risk-based analysis of adverse maternal outcomes yielded a risk of miscarriage of 2.200 (95% CI: 0.584-8.291; P > 0.05). After adjusting the model for each outcome, significant risks of preterm labour, foetal birth restriction, and low birth weight were revealed (P < 0.05). CONCLUSION: Combined preeclampsia has a significantly higher risk of adverse pregnancy outcomes for the foetus.Therefore, the prevention and control of eclampsia in pregnant women should be improved to ensure maternal and neonatal health.

Mitochondrial DNA copy number is associated with incident chronic kidney disease and proteinuria in the AIDS linked to the intravenous experience cohort.

We evaluated the prospective association of mitochondrial DNA copy number (mtDNA CN) with markers of kidney function among a cohort of persons who inject drugs (PWID). This is a Prospective cohort study nested in the AIDS linked to the intravenous experience cohort (community-based cohort of PWID in Baltimore, MD). mtDNA CN was measured at two time-points 5 years apart using a real-time polymerase chain reaction. Kidney function (estimated glomerular filtration rate [eGFR], serum creatinine, urine protein) was measured annually. We used linear mixed effects models to evaluate kidney function trajectories (N = 946) and Cox regression models to assess hazard of incident CKD (eGFR < 60 at two consecutive visits, N = 739) and proteinuria (urine protein:creatinine ratio > 200, N = 573) by level of mtDNA CN (Low [lowest quartile], vs high [other three quartiles]. Models were adjusted for demographic and behavioral characteristics, HIV and/or HCV infection, and comorbidity burden. Low mtDNA CN was independently associated with higher hazard of incident CKD (aHR: 2.33, 95% CI 1.42, 3.80) and proteinuria (aHR: 1.42, 95% CI 1.04, 1.96). Participants with low mtDNA CN had greater declines in eGFR and greater increases in serum creatinine over time. Low mtDNA CN is associated with more rapid kidney function decline and risk of incident CKD and proteinuria.

Evaluating kidney function and the associated risk factors among patients with type 2 diabetes mellitus: a cross-sectional study at a tertiary hospital in Jordan.

BACKGROUND: The diabetes prevalence is escalating in Jordan; as a consequence, the risk of developing diabetic kidney diseases is also increasing. OBJECTIVE: This study evaluated the effect of risk factors and comorbidities on kidney function in patients with type 2 diabetes mellitus (T2DM). DESIGN: A cross-sectional, survey-based study. SETTING: Participants were recruited from the endocrinology and cardiology clinics of a tertiary hospital in Jordan. PARTICIPANTS: Patients with T2DM aged 18 years and more who had undergone a kidney function test within a year before data collection. OUTCOME MEASURES: The estimated GFR (eGFR) mean values and proteinuria presence were used to evaluate the impact of risk factors on kidney function. Descriptive and analytical statistical approaches were used to calculate mean, prevalence and correlations. The SPSS software was used with a p value<0.05 for significance. RESULTS: Of the total 331 study participants, 54.1% were men and 45.9% were women. The mean age was 60 years. The eGFR mean values were significantly reduced in patients with T2DM with hypertension, hyperlipidaemia and proteinuria (p<0.01). The correlation analysis results showed that the eGFR was positively correlated with hypertension and hyperlipidaemia presence (rs=0.253, 0.220), and negatively correlated with age, body mass index and diabetes duration (rs=-0.395, -0.151, -0.221), respectively. However, the eGFR did not corelate with income, sex, smoking and anaemia. Of note, about 68% of the patients with T2DM had uncontrolled diabetes. CONCLUSIONS: Kidney function were severely affected in patients with T2DM in the presence of risk factors and comorbidities. It is highly recommended to control diabetes through medications and life style, and to regularly check for kidney function to halt the deteriorations in kidney function.

Bevacizumab-induced proteinuria and its association with antihypertensive drugs: A retrospective cohort study using a Japanese administrative database.

Proteinuria is a major side-effect of the anti-tumor drug bevacizumab, although its incidence and risk factors in the real world are still unclear. Although renin-angiotensin-aldosterone system inhibitors are used clinically to prevent proteinuria, their efficacy remains unclear. The aim of the present study was to reveal the incidence and risk factors of bevacizumab-induced proteinuria and examine the effectiveness of antihypertensive drugs in preventing proteinuria. We conducted a retrospective cohort study using the National Hospital Organization Clinical Data Archives and Medical Information Analysis Databank. Hospitalized patients who received bevacizumab between January 1, 2016, and June 30, 2019, were included. The study outcome was proteinuria within 12 months of bevacizumab administration. Patient characteristics, laboratory tests, and medications were compared between patients with and without proteinuria using multivariable logistic regression analysis. Among the 2,458 patients, 27% developed proteinuria after bevacizumab administration. Nursing dependence (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.89-3.05; P<0.001) and systolic blood pressure ≥140 mmHg (OR, 1.44; 95% CI, 1.17-1.79; P<0.001) were identified as risk factors. Patients with an estimated glomerular filtration rate (eGFR) of 60-89, 45-59, and <45 mL/min/1.73 m2 had 29.7%, 76.8%, and 66.0% higher odds of proteinuria, respectively, than those with an eGFR ≥90 mL/min/1.73 m2. No significant relationship was observed between antihypertensive drugs and the occurrence of proteinuria. More patients may suffer from proteinuria after bevacizumab administration than previously reported. Nursing dependence and systolic blood pressure are predictive risk factors for bevacizumab-induced proteinuria. Patients at risk of proteinuria should be closely monitored.

Synergistic effect of proteinuria on dipstick hematuria-related decline in kidney function: The Japan Specific Health Checkups (J-SHC) Study.

BACKGROUND: The effect of isolated hematuria without proteinuria on kidney function decline, and the modification by the severity of proteinuria in general population are not fully elucidated. METHODS: Participants were included in the Japan Specific Health Checkups Study between 2008 and 2014. The exposure of interest was the frequency of dipstick hematuria during the observation. In each proteinuria frequency category (non-, occasional, persistent), hematuria-related decline in the eGFR rate was examined by analysis of covariance (ANCOVA). eGFR decline trajectories were also assessed using mixed-effects models. RESULTS: Among the 552,951 participants, 146,753 (26.5%) had hematuria, and 56,021 (10.1%) and 8,061 (1.5%) had occasional and persistent proteinuria, respectively. During the median follow-up of 3.0 years, annual change in eGFR decline in participants with hematuria was significantly faster than in those without hematuria (mean [95% confidence interval]: - 0.95 [- 0.98 to - 0.92] vs - 0.86 [- 0.87 to - 0.84] mL/min/1.73 m2/year; P < 0.001). In ANCOVA, the hematuria-related annual eGFR decline rate increased as proteinuria frequency categories increased (differences in annual eGFR decline rate between participants with and without hematuria: 0.08 [0.06 to 0.09] in participants with non-proteinuria category, 0.17 [0.15 to 0.18] in occasional proteinuria category, and 0.68 [0.65 to 0.71] mL/min/1.73 m2/year in persistent proteinuria category; P for interaction < 0.001). Similar results were obtained by the linear mixed-effect model. CONCLUSIONS: Proteinuria has a synergistic effect on dipstick hematuria-related decline in kidney function. Among the general population without proteinuria throughout the observational period, the "isolated hematuria"-related eGFR decline was statistically significant but the difference was small.

Value of proteinuria in evaluating the severity of HELLP and its maternal and neonatal outcomes.

BACKGROUND: HELLP syndrome refers to a group of clinical syndromes characterized by hemolysis, elevated liver enzymes and low platelet, and the evidence on the association between proteinuria and the severity of HELLP and its maternal and neonatal outcomes is rare. METHODS: 106 pregnant women were assigned to the proteinuric group (24-hUPro ≥ 0.3 g, 79 cases) and the non-proteinuric group (24-hUPro < 0.3 g, 27 cases). The proteinuric group was further divided into three subgroups: mild group (24-hUPro:0.3-2.0 g, 33 cases), moderate group (24-hUPro:2.0-5.0 g, 21 cases) and severe group (24-hUPro: ≥5.0 g, 25 cases). The general clinical data, laboratory indexes, complications and pregnancy outcome and adverse neonatal outcomes of HELLP with or without proteinuric were analyzed. RESULTS: Compared with proteinuric group, the non-albuminuric group or in the three proteinuric subgroups of HELLP pregnant women's, increased proteinuria was associated with earlier onset gestations, higher incidence of abdominal pain, skin jaundice, headache, blurred vision (p < 0.05 respectively), and also the higher levels of ALT, AST, LDH, Fib, APTT, ATII, proportions of tubular urine and lower levels of ALB, PLT (p < 0.05 respectively). In the three subgroups of the proteinuric group, the ratio of fetal growth restriction, cesarean section and postpartum hemorrhage were compared, and the difference was statistically significant (p < 0.05 respectively). Compared with the proteinuric group, the non-proteinuric group had higher birth weight, birth length, and lower SGA, admission rate in NICU (p < 0.05 respectively). In the three subgroups of the proteinuric group, significant differences were identified in the adverse outcomes of newborns (p < 0.05 respectively), and the incidence of adverse outcomes in neonates tended to be higher. Significant differences were identified in birth weight, birth length, and lower SGA and NICU occupancy rate among the three subgroups (p < 0.05 respectively). CONCLUSIONS: HELLP syndrome is a severe complication of pregnancy, involving multiple systems of the whole body. It has posed a great challenge to obstetricians for its acute onset, dangerous condition, rapid progress, and great harm. Thus, insights into HELLP syndrome should be gained, and early diagnosis, early treatment and timely termination of pregnancy should be conducted to reduce the incidence of maternal and fetal adverse outcomes and improve maternal and fetal prognosis.

Morphological study of the placenta in deliveries with pre-eclampsia: Results from a prospective, observational study in India and Pakistan (PURPOSe).

OBJECTIVE: To compare placental findings in women with and without pre-eclampsia. DESIGN: The PURPOSe study included women with stillbirths, women with preterm births and women at term as controls. The placenta of each case was evaluated using the Amsterdam criteria. SETTING: Two sites and five tertiary care hospitals of south Asia (Three in India and two in Pakistan). POPULATION: Pregnancies in India and Pakistan with placental histology including women with documented hypertension and documented proteinuria and women with neither hypertension nor proteinuria. METHODS: We compared the placental findings of the two groups using the Amsterdam criteria and further evaluated the placental findings in women with and without pre-eclampsia who had a stillbirth, preterm live birth, or term live birth (control). MAIN OUTCOME MEASURES: The main outcome measures were the frequency of maternal and fetal vascular malperfusion and the frequency of placental inflammation and its components, chorioamnionitis, funisitis, villitis and intervillitis in women with and without pre-eclampsia. RESULTS: A total of 733 women had pre-eclampsia and 2334 women had neither hypertension nor proteinuria. In the placentas of women with pre-eclampsia, 57.3% had maternal vascular malperfusion compared with 37.1% in women without pre-eclampsia (p < 0.0001). There was not a significant difference in the prevalence of fetal vascular hypertension between mothers with (17.1%) and without (14.8%, p = 0.6118) pre-eclampsia. When placentas were classified as 'histologically normal' or not, 61.3% of those from pre-eclamptic pregnancies were classified as abnormal, whereas if there was no pre-eclampsia, only 45.0% were classified as histologically abnormal (p < 0.0001). We also considered rates of placental maternal vascular malperfusion in women with and without pre-eclampsia with stillbirth, preterm neonatal death, and term live birth. In women at term with no pre-eclampsia, 16.7% of the placentas had features of maternal vascular malperfusion. This occurred in 79.9% of women with stillbirths with pre-eclampsia compared with 51.8% of those without pre-eclampsia. Maternal vascular malperfusion was present in 49.7% of preterm live births with pre-eclampsia compared with 33.8% without pre-eclampsia. We also evaluated the inflammatory lesions by whether the mother had or did not have pre-eclampsia. When all inflammatory lesions were considered, women with pre-eclampsia had significantly fewer inflammatory lesions than those women without pre-eclampsia (17.1% versus 23.6% p = 0.001). Each of the specific inflammatory lesions was less common in placentas of women with pre-eclampsia than those with chorioamnionitis (16.1% versus 21.9%, p = 0.004) and funisitis (1.5% versus. 5.1%, p = 0.0004). CONCLUSIONS: Of placental lesions in women with pre-eclampsia, maternal vascular malperfusion was the most common. Inflammatory lesions were less common in women with pre-eclampsia.