Measurement Of Proteinuria Research Articles

Higher prevalence of kidney function impairment among older people living with HIV in Uganda

BackgroundPeople living with HIV (PLWH) are at risk of kidney function impairment due to HIV-related inflammation, antiretroviral therapy (ART), diabetes mellitus, and hypertension. Older persons may experience a higher burden of chronic kidney disease (CKD) as kidney function declines with increasing age. There is a paucity of data comparing the prevalence of kidney function impairment in older PLWH to that in people without HIV in sub-Saharan Africa.MethodsWe conducted a cross-sectional study among people aged ≥ 60 years living with and without HIV in Kampala, Uganda who were matched 1:1 by community location. We collected data on sociodemographics, comorbidities, and HIV-related clinical characteristics. We defined kidney function impairment as an estimated glomerular filtration rate(eGFR) < 60mls/min/1.73m2 with or without proteinuria. We constructed multivariable logistic regression models to study associations between participant characteristics and kidney function impairment.ResultsWe enrolled 278 people (median age 66 years); 50% were PLWH, and 51.8% were female. Among PLWH, 33.1% (95% CI: 25.7-41.4%) had kidney function impairment versus 12.9% (95% CI: 8.3-19.7%) among people without HIV, (p-value < 0.01). The prevalence of proteinuria among PLWH versus people without HIV was 43.9% (95% CI:35.8-52.3%) versus 19.4% (95% CI:13.6-26.9%) p-value < 0.01. Living with HIV (OR = 3.89(95% CI: 2.04–7.41), p-value < 0.01), older age (OR = 1.13, (95% CI:1.07–1.20), p-value < 0.01), female sex (OR = 1.95, (95% CI:1.06–3.62), p-value = 0.03) and a prior diagnosis of hypertension (OR = 2.19(95% CI:1.02–4.67), p-value = 0.04) were significantly associated with kidney function impairment.ConclusionsHIV infection is strongly associated with kidney function impairment among older PLWH. Prioritizing routine measurements of kidney function and proteinuria in older PLWH will enable early detection and institution of measures to reduce the progression of kidney disease.

Long-Term Follow-Up of Patients with Chronic Kidney Disease: Renal Function Decline and Associated Risk Factors

ABSTRACT Evaluating the chronic course of chronic kidney disease (CKD) and identifying associated risk factors is essential for effective management. This study aims to identify risk factors and monitor the decline in renal function through prolonged follow-up of CKD patients. This retrospective cohort study included 410 CKD patients diagnosed between 2015 and 2022. Data collected included demographics, comorbidities, and repeated measurements of glomerular filtration rate (GFR) and proteinuria. Statistical analyses examined the association between GFR decline and risk factors such as age, diabetes, hypertension, and proteinuria during the follow-up period. The cohort showed a progressive decline in GFR over time. Significant associations were found between GFR decline and age, diabetes, hypertension, and higher proteinuria levels (P &lt; 0.001). Age was associated with a 0.32 ml/min decline in GFR per 1.73 m², while the coefficients for hypertension and diabetes were -2.98 and -4.21, respectively. A strong correlation was found between proteinuria and GFR decline (β = -6.78, P &lt; 0.001). Early identification and management of risk factors are crucial for slowing CKD progression. These findings underscore the need for targeted interventions to preserve renal function and improve patient outcomes.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study

BackgroundChronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries.MethodsA retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months.ResultsOut of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing.ConclusionOur findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Relationship between proteinuria and changes in antepartum and postpartum choroidal thickness in patients with pre-eclampsia

Pre-eclampsia (PE) is a hypertensive disorder characterised by systemic vascular resistance and endothelial dysfunction. It is known to influence choroidal thickness (CT). No previous studies have explored the antepartum and postpartum changes in CT with respect to the protein-creatinine ratio (PCR), a measure of proteinuria that is a clinical hallmark of PE. This study evaluated the correlations between antepartum and postpartum CT and the PCR in patients with PE. In this retrospective study, sixty-six eyes (66 patients) were analysed. The patients were divided into two groups according to the median PCR value (2.36 mg/mg): low PCR group (< 2.36 mg/mg) and high PCR group (≥ 2.36 mg/mg). Ophthalmologic clinical data were collected and assessed. We observed higher antepartum CT and higher mean arterial pressure in high PCR group than in low PCR group. Moreover, postpartum CT decreased significantly in high PCR group. In the multivariate analysis, CT changes were correlated with antepartum CT and antepartum PCR after logarithm transformation. In conclusion, a greater decrease in CT was observed in high PCR group than in low PCR group. Further, the antepartum PCR showed a correlation with the extent of CT reduction.

#850 The association between proteinuria and stroke: results from the non-communicable diseases screening programme of Chiang Mai Region, Northern Thailand

Abstract Background and Aims Stroke is a significant global health issue, representing the second leading cause of death and a major contributor to disability. It can be classified into two main types: ischemic stroke, caused by blockage of a brain blood vessel, and haemorrhagic stroke, resulting from blood vessel rupture. Chronic kidney disease (CKD) is another prevalent health concern, affecting approximately 10% of all populations worldwide. CKD impairs kidney function and has been associated with an increased risk of cerebrovascular events, including stroke. Within the Northern Thai population, the prevalence of CKD is higher than the global average, underscoring the importance of investigating the relationship between CKD and stroke in this region. Method All patients for which accurate proteinuria measurement was obtained as part of the NCD screening program in Chiang Mai, Northern Thailand were included in the study. Multilinear cox regression analysis was used to estimate the hazards ratio for the association between proteinuria on stroke. The model was adjusted for other significant confounders of the association including age, sex, CKD, diabetes, hypertension and hypercholesterolaemia Results In a cohort of 3967 patients for which accurate proteinuria measurements were obtained and for whom had complete data for covariates, there was no evidence for an association between proteinuria and stroke. Hazards ratio for stroke in patients with trace proteinuria (adjusted for covariates) was 1.08 (95% CI 0.80-1.45) and positive proteinuria 0.06 (0.78-1.44) compared to a baseline of no proteinuria. Conclusion This study provides important insights into stroke risk factors in the Northern Thai population. The lack of substantial association between proteinuria and stroke suggests that proteinuria may not independently contribute to stroke risk in this cohort. Generalizability, however, is limited due to overrepresentation of diabetes and hypercholesterolaemia in the cohort, which is a strong independent risk factor for stroke. Increasing age is identified as the most critical risk factor for stroke. Understanding these associations can guide targeted interventions and public health strategies for stroke prevention in this population. The study limitations highlight the importance of analysis of a cohort that is more representative of a wider population in terms of chronic disease, such as diabetes and hypercholesterolaemia, and highlights the importance of longer follow up to fully elucidate whether proteinuria has an association with stroke. Furthermore the study raises questions as to whether measurement of proteinuria via urine dipstick analysis may limit conclusions that can be drawn compared to more robust methods such as urine albumin:creatinine or urine protein:creatinine ratios. Finally this study may be underpowered to detect subtle changes of a hazards ratio of less than 1.2, so is at risk of a type 2 statistical error.

#559 Validation of the Kidney Failure Risk Equation (KFRE) in individuals with chronic kidney disease and multimorbidity

Abstract Background and Aims Increasing numbers of individuals with chronic kidney disease (CKD) experience multiple long-term conditions (multimorbidity). Clinical guidance recommends the use of validated risk prediction equations, such as the kidney failure risk equation (KFRE), to guide referral to specialist kidney care services. However, multimorbidity may impact the accuracy of creatinine-based eGFR and bias the prognostic utility of KFRE. Equations with alternative filtration markers, such as Cystatin C eGFR (eGFRcys) or the combined creatinine and Cystatin C eGFR (eGFRcrcys), may improve KFRE's risk stratification and discrimination of future kidney failure risks. This study aimed to validate the four-variable KFRE in individuals with CKD, with and without multimorbidity in a research-based cohort (UK Biobank) and a population-based cohort (Stockholm Creatinine Measurements project (SCREAM)). The study also assessed the performance of KFRE when using eGFRcr, eGFRcys and eGFRcrcys. Method Individuals from both cohorts were included if they had CKD, defined as eGFR&amp;lt;60 mL/min/1.73 m2 by any of the three eGFR equations (eGFRcr, eGFRcys and eGFRcrcys), and had available proteinuria measurement at time of testing or within the previous 12 months. Multimorbidity was defined as the presence of two or more long-term conditions in addition to CKD and was grouped into multimorbidity clusters based on previous research. The outcome was kidney failure, defined as the need for long-term dialysis or kidney transplantation. KFRE performance at 2- and 5-years was assessed using the area under the receiver operating characteristic curve and c-index for discrimination and calibration curves for calibration. Results We included 24 489 individuals from UK Biobank and 42 902 individuals from SCREAM (mean age 62.8 (SD 5.6) and 70.1 (SD14.1), 54% and 66% female, respectively). In UK biobank, 14 998 individuals had multimorbidity, of which 5 375 had cardiometabolic multimorbidity. In SCREAM, 30 147 had multimorbidity and 17 854 cardiometabolic multimorbidity. Overall, there were 252 and 312 kidney failure events and 1 108 and 1 471 death events in UK Biobank and 918 and 1 098 kidney failure events and 8 785 and 10 152 death events in SCREAM within 2- and 5-years respectively. Model performance was consistent across both cohorts. Discrimination power of KFRE was good in individuals with and without multimorbidity and across the 2-year and 5-year models (Table 1). Calibration plots revealed over-estimation of risk at 2-years in both cohorts and under-estimation of risk at 5-years in patients with multimorbidity in UK Biobank. There was no improvement in model performance when using eGFRcys or eGFRcrcys compared to eGFRCr. There was a higher cumulative incidence of both kidney failure and death in the multimorbidity group, with a prominent increase in risk of death over time compared to the no multimorbidity group. This was most evident in the SCREAM cohort (Fig. 1). Conclusion KFRE adequately predicts kidney failure in individuals with multimorbidity and either creatinine or cystatin C can be used. Given the high rates of mortality amongst people with multimorbidity, exploration of models that account for the competing risk of death is warranted.

#2908 Renal progenitor cells an early non-invasive biomarker of silent kidney injury in Fabry disease

Abstract Background and Aims Fabry's disease (FD), a hereditary condition, is linked to the X chromosome due to a mutation in the gene encoding alpha-galactosidase A (alpha-GalA). This mutation results in a defect in the metabolism of glycosphingolipids, leading to the deposition of globotriaosylceramide (GB3) primarily in organs such as the heart, kidneys, and nervous system. Renal injury can affect any level of the structure, with the podocytes being the most commonly affected due to their low regeneration and high contact with GB3. This leads to proteinuria, and if it exceeds 0.5 g, it is associated with a rapid deterioration of renal function. Renal assessment is carried out through blood analysis, proteinuria measurement, ultrasound, and the gold standard, renal biopsy. However, there is a growing trend towards less invasive biomarkers such as lysoGB3 titration in blood and urine, podocyturia, or renal progenitor cells (RPCs) in renal biopsy material or cell culture. RPCs possess self-renewal, clonogenicity, and multidifferentiation properties, contributing to cellular remodeling. They express specific markers like CD133/CD24 and CD106 in the parietal epithelium of Bowman's capsule. It is known that GB3 expresses CD77. The proliferative response of RPCs can become dysregulated, leading to detachment and elimination in the urine. The aim of the study was to demonstrate the presence of renal progenitor cells (RPCs) in urine as a non-invasive early marker for detecting renal damage in patients with Fabry's disease (FD) and to establish a correlation between RPC presence, GB3 deposition, and their potential association with the degree of renal injury. Method It is an open observational, case-control, single-center study on the urine of patients with Fabry's disease (FD) considered as cases, patients without a history considered as healthy controls, and patients with non-FD renal disease such as Gittelman syndrome or another biopsy-proven cause as positive controls. Renal progenitor cells (RPCs) were isolated using specific markers and flow cytometry, correlating these findings with renal function and albuminuria. Results A total of 75 recent urine samples were processed, corresponding to 59 patients: 16 with Fabry's disease (FD), 11 with Gittelman syndrome, 10 with chronic kidney disease (CKD), and 22 healthy controls. The samples were divided for sediment and microalbuminuria analysis, and separately for the isolation of renal progenitor cells (RPCs). The classification and quantification of the isolated cell types were performed, establishing positivity points using compensation panels with CD3 lymphocyte markers. This was followed by the identification of RPCs through positivity for CD133+/CD24+, CD106+, and CD106– markers. Once RPCs were identified, GB3 marking was carried out using CD77+. Differences were observed among the analyzed patient groups. In healthy controls, there was minimal or no presence of renal progenitor cells (RPCs), except in two patients where isolation was repeated in three different samples, maintaining positivity. Subsequent diagnoses revealed bilateral lithiasis and previously unknown hypertension in these cases. Patients with Gittelman syndrome showed a higher quantity of RPCs compared to healthy controls, but with P &amp;gt; .05. However, clear RPCs positivity was evident in patients with Fabry's disease (FD) and chronic kidney disease (CKD) confirmed by biopsy, with P &amp;lt; .05. Additionally, differences in the number of RPCs were noted based on the degree of renal disease when correlated with the presence of proteinuria &amp;lt; 0.5 g and &amp;gt; 0.5 g, with P &amp;lt; .05. Conclusion With these results, we can conclude that renal progenitor cells (RPCs) may serve as an early biomarker for silent renal injury of various etiologies. Furthermore, if we perform labeling with CD77, we can attribute it to the deposition of GB3 in Fabry's disease (FD).

#1392 MEST-C score correlation with proteinuria reduction after SGLT2i treatment in patients with IgA nephropathy

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcomes and with nephroprotection independent of diabetes status. Recent data suggest that SGLT2i significantly reduce proteinuria in patients with IgA nephropathy (IgAN). Data available for the use of the MEST-C score to determine if treatment would benefit IgAN patients is scarce. The aim of our study was to assess the degree of proteinuria reduction after SGLT2i treatment in IgAN and its possible association with the MEST-C score. Method 63 adult patients with biopsy-proven IgA nephropathy, eGFR ≥ 30 mL/min/1.73 m2 (CKD-epi), and total urine protein of &amp;gt;0.5 grams/day at screening were included. Patients with secondary IgAN and crescents were excluded. All receiving maximally tolerated RASi for at least 12 weeks. All patients started dapagliflozin 10 mg once per day after baseline data were registered. The total follow-up was 12 months. The main outcome was the decline in eGFR and the reduction in 24-hour proteinuria from SGLT2i initiation to 1,3, 6, 9, 12 months, end-stage renal disease, or kidney or cardiovascular death. Three repeated measurements of proteinuria (mg/24H) were performed, 90 days before SGLT2i treatment initiation, and only patients with stable proteinuria were enrolled in the study. Results 49 patients (35/14 M/F), with mean age of 41,9 ± 19,6 years, completed follow up. 8 patients discontinued treatment due to adverse events attributed to dapagliflozin. At baseline eGFR was 68.21±18,1 ml/min/1.73 m2 and Upr: 2196±1091 mg/24H. The MEST-C scores were correlated with the serum creatinine level, proteinuria, and hematuria. The mean serum creatinine level was higher in M1, E1, S1, and T1 compared with score “0”. It was statistically significant (p = 0.03) only in the T-score. The mean proteinuria level was again higher in M1, S1, and T1 but reached statistical significance (p = 0.037) in only the T1-score. E1 has higher hematuria. The Upr/24H difference for dapagliflozin was −24.7% (95% CI −27.5, −23.2; p &amp;lt; 0.001) at the end of follow-up (month 12). Proteinuria reduction was similar across all eGFRs, age, and baseline proteinuria. Among MEST-C score parameters, T1 had a negative impact on the antiproteinuric effect of dapagliflozin (p = 0.01) No hypoglycemic events were reported and no deaths occurred. Conclusion In the present study, the use of SGLT2i was associated with a significant reduction of proteinuria in patients with IgA nephropathy and maximally tolerated RASi. We analyzed renal outcomes in association with pathologic features. We established that the presence of the T1 score has a negative impact on proteinuria reduction after SGLT2i treatment. Further studies are needed to investigate the impact of the use of the Oxford Classification score for developing individual treatment therapies.

#876 Albuminuria and the risk of dementia and different dementia subtypes: the Stockholm Creatinine Measurements (SCREAM) project

Abstract Background and Aims Studies investigating the association of chronic kidney disease and dementia predominantly focused on estimated glomerular filtration rate (eGFR) rather than albuminuria. The few studies focusing on albuminuria reported conflicting results, probably due to a lack of power, not taking into account the different dementia subtypes, not adjusting for eGFR, and the use of different albuminuria measurement techniques. This study therefore investigated the eGFR-independent risk of all-cause and type-specific dementia associated with albuminuria, quantified as urine albumin-creatinine ratio (ACR) and by dipstick, in a large population. Method We included subjects from the Stockholm Creatinine Measurements (SCREAM) project without a history of dementia and with age ≥65 years. The main analyses involved 138 688 subjects with at least one ACR test, and for sensitivity analyses, we involved 170 572 subjects with at least one dipstick proteinuria test. Albuminuria was quantified as KDIGO albuminuria A1-A3 stages. The primary outcome was incidence of all-cause dementia, and the key secondary outcomes were incidence of type-specific dementia. Dementia incidence was ascertained by record linkage with the national dementia registry (SveDem). ICD-10 coding was also used to classify subtypes only when there were no available dementia records in SveDem. Multivariable Cox regression models were used to calculate hazard ratios (HRs, 95% CIs) crude, and adjusted for confounders including baseline eGFR. Results During a median follow-up of 3.9 (IQR, 1.8-7.2) years, 9 970 subjects developed de novo dementia. After multivariable adjustment including baseline eGFR, subjects with an ACR of 30-299 mg/g or ≥300 mg/g had a 26% (HR, 1.26; 95% CI, 1.20-1.32) and 36% (HR, 1.36; 95% CI, 1.24-1.50) higher risk of developing all-cause dementia, respectively, when compared to subjects with an ACR &amp;lt;30 mg/g. Subjects with an ACR of 30-299 mg/g also presented a higher risk of developing several type-specific dementia, including Alzheimer's dementia (HR, 1.09, 95% CI, 1.01-1.17), vascular dementia (HR, 1.35, 95% CI, 1.22-1.48), and unspecified dementia (HR, 1.54, 95% CI, 1.41-1.69). No significant associations between albuminuria and the incidence of Lewy body dementia and Parkinson's Disease with dementia, frontotemporal dementia, as well as other types of dementia were observed. These results were generally robust in several sensitivity analyses, including replicating our main analyses in subjects with a dipstick proteinuria test instead of an ACR. Conclusion Increased albuminuria is associated with a higher risk of all-cause, Alzheimer's, and vascular dementia, independent of baseline eGFR and different albuminuria measurement techniques.

#817 Genetic analysis in a group of patients with persistent isolated microscopic hematuria

Abstract Background and Aims Autosomal dominant Alport syndrome (ADAS) is a genetic disease caused by pathogenic variants in COL4A3 and COL4A4 genes. ADAS is the main cause of isolated persistent microscopic hematuria (PMH). However, other diseases like IgA nephropathy (IgAN) can present with PMH. Establishing a precise genetic diagnosis in this type of patients would avoid invasive studies like kidney biopsies. In this study we performed a comprehensive genetic test in a cohort of patients with isolated PMH to evaluate the frequency of ADAS or other genetic abnormalities and compare the clinical characteristics of patients with or without ADAS Method Fifty-two patients with PMH were included in the study. PMH was defined by the presence of 3 or more dysmorphic red blood cells per field in at least 5 consecutive urine sediments and a time-averaged proteinuria &amp;lt;1 gr/day. Average proteinuria was determined for every 6 months of follow-up and time-averaged (TA) proteinuria represented an average of the mean proteinuria measurements in each 6-month period. A comprehensive genetic study using whole exome next-generation sequencing was performed. One hundred and one genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney diseases were analyzed. Patients with known secondary causes of hematuria were excluded. The baseline clinical characteristics of patients with and without ADAS were compared. Patients with pathogenic variants in COL4A5 gene were excluded of this analysis. Results Thirty-one (60%) patients were diagnosed with ADAS (16 patients with pathogenic variants in COL4A3, 15 in COL4A4), 3 (6%) patients (2 women, 1 man) presented pathogenic variant in COL4A5 gene, and the genetic study was negative in the remaining 18 patients (variants of unknown significance in COL4A3 or COL4A4 were found in 3 of the latter). No other genetic abnormalities were detected in the panel of 101 genes. Table 1 shows the baseline clinical characteristics of patients with and without ADAS. Patients with ADAS presented a higher TA proteinuria [0.23 (0.11-0.6) vs 0.08 (0.05-0.16), p = 0.01], and a more frequent familial history of isolated microscopic hematuria (76% vs 40%, p = 0.01) chronic kidney disease (CKD) (44% vs 0%, p = 0.01) or end stage kidney disease (32% vs 0%, p = 0.02). In the multivariate analysis, only a family history of microscopic hematuria was associated with ADAS: OR 5.62 (1.25-25.49, p = 0.02). Conclusion ADAS is the most common cause of PMH. A genetic study should be the first diagnostic step in order to obtain a precise cause of the disease and avoid invasive procedures. A family history of microscopic hematuria and of CKD increases the likelihood of ADAS prior to the performance of genetic test.

The utility of phospholipase A2 receptor antibody in pregnancy: A case report

Primary membranous nephropathy remains a rare but challenging condition to manage in pregnancy. We present a case of an unplanned pregnancy in a 35-year-old woman with PLA2R-antibody positive membranous nephropathy, who had demonstrated serological response to rituximab given three months prior to pregnancy (PLA2R 115 IUmL reducing to 2 IU/mL, normal &lt;13.9 IU/mL)). Throughout pregnancy, serial measurements of proteinuria and PLA2R-antibodies were used to understand disease activity and inform the decision to escalate treatment. Delivery of a healthy male infant occurred at 34 weeks, due to threatened pre-eclampsia and reduced fetal growth. There was evidence of trans-placental transfer of antibodies (15.2 IU/mL – normal &lt;13.9 IU/mL) but no associated nephrotic syndrome in the infant. This case highlights the potential of PLA2R antibody as a diagnostic and monitoring tool during pregnancy, and adds to a small body of literature around the consequences of fetal–maternal transfer of the PLA2R antibody.

Higher prevalence of kidney function impairment among older people living with HIV in Uganda.

People living with HIV (PLWH) are at risk of kidney function impairment due to HIV-related inflammation, antiretroviral therapy (ART), diabetes mellitus, and hypertension. Older persons may experience a higher burden of chronic kidney disease (CKD) as kidney function declines with increasing age. There is a paucity of data comparing the prevalence of kidney function impairment in older PLWH to that in HIV-uninfected people in sub-Saharan Africa. We conducted a cross-sectional study among people aged ≥ 60 years living with and without HIV in Kampala, Uganda who were matched 1:1 by community location. We collected data on sociodemographics, comorbidities, and HIV-related clinical characteristics. We defined kidney function impairment as an estimated glomerular filtration rate(eGFR) < 60mls/min/1.73m2 with or without proteinuria. We constructed multivariable logistic regression models to study associations between participant characteristics and kidney function impairment. We enrolled 278 people (median age 66 years); 50% were PLWH, and 51.8% were female. Overall, the prevalence of kidney function impairment was 23.0% (95% CI:18.4%-28.4%); 33.1% (95% CI: 25.7%-41.4%) versus 12.9% (95% CI: 8.3%-19.7%) among people living with and without HIV (p-value < 0.01). The prevalence of proteinuria among PLWH versus people without HIV was 43.9% (95% CI:35.8%-52.3%) versus 19.4% (95% CI:13.6%-26.9%) p-value < 0.01. Living with HIV (OR = 3.89(95% CI: 2.04-7.41), p-value < 0.01), older age (OR = 1.13, (95% CI:1.07-1.20), p-value < 0.01), female sex (OR = 1.95, (95% CI:1.06-3.62), p-value = 0.03) and a prior diagnosis of hypertension (OR = 2.19(95% CI:1.02-4.67), p-value = 0.04) were significantly associated with kidney function impairment. HIV infection is strongly associated with kidney function impairment among older PLWH. Prioritizing routine measurements of kidney function and proteinuria in older PLWH will enable early detection and institution of measures to reduce the progression of kidney disease.

Laboratory-based surveillance of chronic kidney disease in people with private health coverage in Brazil

BackgroundAlthough approximately 25% of Brazilians have private health coverage (PHC), studies on the surveillance of chronic kidney disease (CKD) in this population are scarce. The objective of this study was to estimate the prevalence of CKD in individuals under two PHC regimes in Brazil, who total 8,335,724 beneficiaries.MethodsOutpatient serum creatinine and proteinuria results of individuals from all five regions of Brazil, ≥ 18 years of age, and performed between 10/01/2021 and 10/31/2022, were analyzed through the own laboratory network database. People with serum creatinine measurements were evaluated for the prevalence and staging of CKD, and those with simultaneous measurements of serum creatinine and proteinuria were evaluated for the risk category of the disease. CKD was classified according to current guidelines and was defined as a glomerular filtration rate (GFR) < 60 ml/min/1.73 m² estimated by the 2021 CKD-EPI equation.ResultsThe number of adults with serum creatinine results was 1,508,766 (age 44.0 [IQR, 33.9–56.8] years, 62.3% female). The estimated prevalence of CKD was 3.8% (2.6%, 0.8%, 0.2% and 0.2% in CKD stages 3a, 3b, 4 and 5, respectively), and it was higher in males than females (4.0% vs. 3.7%, p < 0.001, respectively) and in older age groups (0.2% among 18-29-year-olds, 0.5% among 30-44-year-olds, 2.0% among 45-59-year-olds, 9.4% among 60-74-year-olds, and 32.4% among ≥ 75-year-olds, p < 0.001) Adults with simultaneous results of creatinine and proteinuria were 64,178 (age 57.0 [IQR, 44.8–67.3] years, 58.1% female). After adjusting for age and gender, 70.1% were in the low-risk category of CKD, 20.0% were in the moderate-risk category, 5.8% were in the high-risk category, and 4.1% were in the very high-risk category.ConclusionThe estimated prevalence of CKD was 3.8%, and approximately 10% of the participants were in the categories of high or very high-risk of the disease. While almost 20% of beneficiaries with PHC had serum creatinine data, fewer than 1% underwent tests for proteinuria. This study was one of the largest ever conducted in Brazil and the first one to use the 2021 CKD-EPI equation to estimate the prevalence of CKD.

Reference intervals for selected blood and urinary parameters related to renal function in clinically healthy ferrets (Mustela putorius furo)

BackgroundDiagnosis of chronic kidney disease can be challenging in ferrets. Physiological creatinine values are lower than in dogs and cats and marked elevations may only be detected in advanced disease. In canine and feline patients, specific staging, and treatment guidelines are available, based on serum creatinine, symmetric dimethylarginine (SDMA) levels, presence of proteinuria, and blood pressure measurement. No such guidelines exist for ferrets, and there is a lack of data concerning certain laboratory parameters. MethodsBlood and urine samples were taken from 60 clinically healthy pet ferrets to establish species-specific reference intervals for serum SDMA and urine protein/creatinine ratio (UPC ratio). Liquid-chromatography tandem mass spectrometry (HPLC-MS) was used for determination of serum SDMA, a colorimetric spectrophotometric method for urinary protein and an enzymatic method for urine creatinine. ResultsThe calculated reference interval for serum SDMA (2.78–7.66 µg/dL) was found to be lower than in dogs and cats, while the UPC ratio is similar to dogs (<0.5). Conclusions and clinical relevanceSerum SDMA reference intervals for ferrets may be lower than internals published for dogs and cats, while the UPC ratio appears to be similar to the ratio for dogs.

Urinary Biomarkers for Lupus Nephritis: A Systems Biology Approach.

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder. Kidney involvement, termed lupus nephritis (LN), is seen in 40-60% of patients with systemic lupus erythematosus (SLE). After the diagnosis, serial measurement of proteinuria is the most common method of monitoring treatment response and progression. However, present treatments for LN-corticosteroids and immunosuppressants-target inflammation, not proteinuria. Furthermore, subclinical renal inflammation can persist despite improving proteinuria. Serial kidney biopsies-the gold standard for disease monitoring-are also not feasible due to their inherent risk of complications. Biomarkers that reflect the underlying renal inflammatory process and better predict LN progression and treatment response are urgently needed. Urinary biomarkers are particularly relevant as they can be measured non-invasively and may better reflect the compartmentalized renal response in LN, unlike serum studies that are non-specific to the kidney. The past decade has overseen a boom in applying cutting-edge technologies to dissect the pathogenesis of diseases at the molecular and cellular levels. Using these technologies in LN is beginning to reveal novel disease biomarkers and therapeutic targets for LN, potentially improving patient outcomes if successfully translated to clinical practice.

The mother during pregnancy and the puerperium: Detailed data abstracted from the clinical obstetric records of ALSPAC pregnancies

Background When the Avon Longitudinal Study of Parents and Children (ALSPAC) was planned, it was assumed that the clinical obstetric data would be easily accessible from the newly developed National Health Service computerised ‘STORK’ system. Pilot studies, however, showed that, although fairly accurate in regard to aspects of labour and delivery, it was, at the time (1990-2), inadequate for identifying the full antenatal and postnatal details of clinical complications and treatments of the women in the Study. Methods A scheme was therefore developed to train research staff to find and abstract relevant details from clinical records onto proformas designed for the purpose. Extracting such data proved very time consuming (up to six hours for complicated pregnancies) and consequently expensive. Funding for the enterprise was obtained piecemeal using specific focussed grants to extract data for subsamples of the Study, including a random sample to serve as controls. Results To date, detailed records have been completed for 8369 pregnancies, and a further 5336 (13,705 in total) have complete details on specific prenatal areas, including serial measures of maternal blood pressure, proteinuria and weight. In this Data Note we describe the information abstracted from the obstetric medical records concerning the mother during pregnancy, labour, delivery and the first two weeks of the puerperium. Information abstracted relating to the fetus (including fetal monitoring, presentation, method of delivery) and neonate (signs of asphyxia, resuscitation, treatment and well-being) have been described in a further Data Note. Conclusions These data add depth to ALSPAC concerning ways in which the signs and symptoms, procedures and treatments of the mother prenatally, intrapartum and postnatally, may impact on the long-term health and development of both mother and child. They augment the data collected from the mothers’ questionnaires (described elsewhere) and the ‘STORK’ digital hospital data.

Use of kidney failure risk equation as a tool to evaluate referrals from primary care to specialist nephrology care.

With rising costs and burden of chronic kidney disease (CKD), timely referral of patients to a kidney specialist is crucial. Currently, Kidney Health Australia (KHA) uses a 'heat map' based on severity and not future risk of kidney failure, whereas the kidney failure risk equation (KFRE) score predicts future risk of progression. Evaluate whether a KFRE score assists with timing of CKD referrals. Retrospective cohort of 2137 adult patients, referred to tertiary hospital outpatient nephrologist between 2012 and 2020, were analysed. Referrals were analysed for concordance with the KHA referral guidelines and, with the KFRE score, a recommended practice. Of 2137 patients, 626 (29%) did not have urine albumin-to-creatinine ratio (UACR) measurement at referral. For those who had a UACR, the number who met KFRE preferred referral criteria was 36% less than KHA criteria. If the recommended KFRE score was used, then fewer older patients (≥40 years) needed referral. Positively, many diabetes patients were referred, even if their risk of kidney failure was low, and 29% had a KFRE over 3%. For patients evaluated meeting KFRE criteria, a larger proportion (76%) remained in follow-up, with only 8% being discharged. KFRE could reduce referrals and be a useful tool to assist timely referrals. Using KFRE for triage may allow those patients with very low risk of future kidney failure not be referred, remaining longer in primary care, saving health resources and reducing patients' stress and wait times. Using KFRE encourages albuminuria measurement.

External Validation of the Kidney Failure Risk Equation Among Urban Community-Based Chinese Patients With CKD

Rationale & ObjectiveThe Kidney Failure Risk Equation has been proved to perform well in multinational databases, while lacking validation in Asian populations. This study sought to externally validate the equations in a community-based chronic kidney disease cohort in China. Study DesignA retrospective cohort study. Setting & ParticipantsPatients with estimated glomerular filtration rate (eGFR)<60 ml/min/1.73m2 dwelling in an industrialized coastal city of China. ExposureAge, sex, eGFR and albuminuria in the 4-variable model, while adding serum calcium, phosphate, bicarbonate and albumin in the 8-variable model. OutcomeInitiation of chronic dialysis treatment. Analytical ApproachModel discrimination, calibration and clinical utility were evaluated by Harrell’s C-statistic, calibration plots and decision curve analysis, respectively. ResultsA total of 4587 participants were enrolled for the validation of the 4-variable model, while 1414 for the 8-variable one. The median time of follow-up were 4.0 (interquartile range: 2.6-6.3) years for the 4-variable model and 3.4 (2.2-5.6) years for the 8-variable one. For the 4-variable model, the C-statistics were 0.750 (95% confidence interval: 0.615-0.885) for the 2-year model and 0.766 (0.625-0.907) for the 5-year one, while 0.756 (0.629-0.883) and 0.774 (0.641-0.907), respectively, for the 8-variable ones. Calibration was acceptable for both the 4-variable and 8-variable models. Decision curve analysis for the models in 5-year scale performed better throughout different net benefit thresholds than the eGFR-based (<30 ml/min/1.73m2) strategy. LimitationsA large proportion of patients lack albuminuria measurement and only a subset of population could provide complete data for the 8-variable equation. ConclusionsKidney Failure Risk Equation showed acceptable discrimination and calibration and better clinical utility than the eGFR-based strategy for incidence of kidney failure among community-based urban Chinese patients with chronic kidney disease.

Autoimmune and neuropsychiatric phenotypes in a Mecp2 transgenic mouse model on C57BL/6 background.

Systemic Lupus Erythematosus (SLE) impacts the central nervous system (CNS), leading to severe neurological and psychiatric manifestations known as neuropsychiatric lupus (NPSLE). The complexity and heterogeneity of clinical presentations of NPSLE impede direct investigation of disease etiology in patients. The limitations of existing mouse models developed for NPSLE obstruct a comprehensive understanding of this disease. Hence, the identification of a robust mouse model of NPSLE is desirable. C57BL/6 mice transgenic for human MeCP2 (B6.Mecp2Tg1) were phenotyped, including autoantibody profiling through antigen array, analysis of cellularity and activation of splenic immune cells through flow cytometry, and measurement of proteinuria. Behavioral tests were conducted to explore their neuropsychiatric functions. Immunofluorescence analyses were used to reveal altered neurogenesis and brain inflammation. Various signaling molecules implicated in lupus pathogenesis were examined using western blotting. B6.Mecp2Tg1 exhibits elevated proteinuria and an overall increase in autoantibodies, particularly in female B6.Mecp2Tg1 mice. An increase in CD3+CD4+ T cells in the transgenic mice was observed, along with activated germinal center cells and activated CD11b+F4/80+ macrophages. Moreover, the transgenic mice displayed reduced locomotor activity, heightened anxiety and depression, and impaired short-term memory. Immunofluorescence analysis revealed IgG deposition and immune cell infiltration in the kidneys and brains of transgenic mice, as well as altered neurogenesis, activated microglia, and compromised blood-brain barrier (BBB). Additionally, protein levels of various key signaling molecules were found to be differentially modulated upon MeCP2 overexpression, including GFAP, BDNF, Albumin, NCoR1, mTOR, and NLRP3. Collectively, this work demonstrates that B6.Mecp2Tg1 mice exhibit lupus-like phenotypes as well as robust CNS dysfunctions, suggesting its utility as a new animal model for NPSLE.

An increase in albuminuria is associated with a higher incidence of malignancies.

A single albuminuria measurement is reported to be an independent predictor of cancer risk. Whether change in albuminuria is also independently associated with cancer is not known. We included 64303 subjects of the Stockholm CREAtinine Measurements (SCREAM) project without a history of cancer and with at least two urine albumin-creatinine ratio (ACR) tests up to 2 years apart. Albuminuria changes were quantified by the fold-change in ACR over 2 years, and stratified into the absence of clinically elevated albuminuria (i.e. never), albuminuria that remained constant, and albuminuria that increased or decreased. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidences. During a median follow-up of 3.7 (interquartile range 3.6-3.7) years, 5126 subjects developed de novo cancer. After multivariable adjustment including baseline estimated glomerular filtration rate and baseline ACR, subjects with increasing ACR over 2 years had a 19% (hazard ratio 1.19; 95% confidence interval 1.08-1.31) higher risk of overall cancer compared with those who never had clinically elevated ACR. No association with cancer risk was seen in the groups with decreasing or constant ACR. Regarding site-specific cancer risks, subjects with increasing ACR or constant ACR had a higher risk of developing urinary tract and lung cancer. No other associations between 2-year ACR changes and site-specific cancers were found. Increases in albuminuria over a 2-year period are associated with a higher risk of developing overall, urinary tract and lung cancer, independent of baseline kidney function and albuminuria. These data add important weight to the link that exists between albuminuria and cancer incidence.