bluuebunny/crossref_metadata_2025 huggingface dataset:
#1694 The Cl-/HCO3-ratio as a predictor of decompensated metabolic acidosis in CKD stages G4 and G5
Authors: Gołębiowski Tomasz , Korus Justyna , Banasik Miroslaw , Szymczak Maciej
Published: May 2024

Background and Aims

Metabolic acidosis (MA) is a common disorder in patients with chronic kidney disease (CKD) and is associated with both a normal anion gap (AGMA) and a high anion gap (HAGMA). AGMA is typically detected early in the course of CKD, whereas HAGMA appears later in the course of CKD due to the accumulation of non-chloride anions such as phosphate, sulphate, and an array of organic acids. The anion gap (AG) is usually calculated as the difference between serum concentration of cations and anions using the formula AG=Na+-(Cl−+HCO3−). The most important anions in serum are chlorides (Cl−) and bicarbonates (HCO3−). The more advanced the CKD, the higher the AG. As eGFR decreases, a reciprocal decrease in HCO3− and an increase in chloride concentration is observed to correct the AG. The aim of this study is to determine whether the Cl−/HCO3− ratio can be used to predict decompensated metabolic acidosis with pH decline in CKD stages G4 and G5.

Method

A total of 115 patients (median age 63 ± 17 years), with CKD stage G4 or G5 were enrolled in this cross-sectional study. Demographic and comorbidity data was obtained from medical records, and the Charlson Comorbid Index (CCI) was calculated. A two-year clinical follow-up was conducted to assess the clinical status of each patient. The number of patients, the time dialysis was started, and deaths were all recorded. All patients were qualified for arteriovenous fistula creation in predialysis period. The arterial (A) and venous (V) blood samples were taken during surgery, directly after vessel dissection, and evaluated in a point of care testing analyzer (POCT). The ratio of arterial Cl− and HCO3− concentration were calculated. According to mean arterial pH (pH-A) the group was divided into Group A pH-A<7.33 and Group B pH-A≥7.33 (Table 1).

Results

In Group A was significantly lower pH-A, pH-V, HCO3−-A, HCO3−-V, pCO2-A, pCO2-V, and significantly higher both arterial and venous Cl− and the Cl−/HCO3− ratios compared to Group B. No such differences were observed in the case of AG. Cl−/HCO3−-A ratio negatively correlated with pH (r = −0.77, p < 0.01) (Fig. 1A). The discriminative power of Cl−/HCO3−-A ratio for predicting pH-A≤7.33 was 0.917 (95% confidence interval [CI] = 0.87–0.97; p < 0.01) which provided 87% sensitivity and 84% specificity (Fig. 1B). The best cut-off was 6.22 (mmol/l)/(mmol/l).

Conclusion

The Cl−/HCO3− ratio lower than 6.22 (mmol/l)/(mmol/l) may be used as predictor of decompensated metabolic acidosis.
#3029 Vitamin D-binding protein: a candidate biomarker for CKD progression
Authors: Gaipov Abduzhappar , Makhammajanov Zhalaliddin , Kabayeva Assem , Tarlykov Pavel , Turebekov Duman
Published: May 2024

Background and Aims

The toxic effects of filtered proteins on the tubules cause a more rapid progression of disease in individuals with higher levels of proteinuria, suggesting the presence of “high-risk candidate” proteins that could contribute to CKD progression. In our previous cross-sectional proteomic study, vitamin D-binding protein (VTDB) showed a significant association with kidney function. However, its persistent expression as a urinary protein in CKD patients remains unknown. Therefore, our aim was to investigate the persistent expression of VTDB in CKD patients and healthy controls during the follow-up period.

Method

The urinary proteomics was investigated using liquid chromatography-mass spectrometry in 18 follow-up CKD patients with stages 1-3 and 15 follow-up healthy individuals. Data analysis was performed by Mascot-SwissProt and STATA software. Parametric and nonparametric statistics were used to analyze results and the relationship between baseline characteristics and proteomic profile. Exponentially Modified Protein Abundance Index (emPAI) was used to estimate peptide count of proteins.

Results

The participant's baseline characteristics are presented in Table 1. The median (IQR) follow-up time for all participants was 368 (250-472) days. A statistically significant difference was found in the initial emPAI of VTDB between the HC and CKD groups. However, there was no statistically significant difference in the follow-up emPAI of VTDB between the two groups. Notably, emPAI values of VTDP decreased over the follow-up period compared to the initial values.

Correlation analysis (Table 2) showed that the elevated levels of urinary VTDB emPAI are associated with decreased levels of initial and follow-up eGFR. A higher negative percentage change (a decline in eGFR over time) was also associated with elevated levels of VTDB protein over the follow-up period. Also, urinary VTDP protein has demonstrated a significant positive correlation with 24 h proteinuria.

Conclusion

In this proteomics study cohort, we observed persistent expression of urinary VTDB protein during the follow-up period in CKD patients compared to healthy controls. Additionally, a statistically significant negative correlation between VTDB protein and eGFR was observed. These findings need further validation using different measurement tools for urinary VTDB assessments and in a larger cohort of CKD patients.

Declaration

We have no conflict of interest to disclose.
#2934 The risk of APOL1 variants in the development of ESKD—a case-control study among cohorts of ESKD with HIV and non-ESKD with and without HIV
Authors: Mooko Teboho , Bisiwe Busiswa , Marx Gerda , Chikobvu Perpetual , Morobadi Daniel , Kemp Gabre , Goedhals Dominique , Nyaga Martin , Mofokeng Thabiso , Ndlovu Kwazi
Published: May 2024

Background and Aims

Apolipoprotein 1 (APOL1) renal allelic risk variants are common in kidney disease patients of African ancestry. This study evaluated the prevalence of APOL1 variants and their influence on end-stage kidney failure (ESKD) and non-ESKD HIV-positive and HIV-negative study cohorts.

Method

This case‒control study enrolled 60 HIV-positive ESKD cases and 160 non-ESKD (80 HIV-positive and 80 HIV-negative) as controls. Participants’ demographic and clinical information and laboratory data as well as blood samples were collected. Genomic DNA was extracted, and purified, and APOL1 risk variants genotyped using TaqMan® predesigned commercial assays.

Results

Study participants in the case and two control cohorts were enrolled with a median age of 42.8 (IQR,38.47-48.57), 41 (IQR,37-46.5), and 41 (IQR,37–47) years, respectively; the frequencies of APOL1 risk variants (G1: rs73885319 and rs60910145 and G2: rs71785313) were 21.8% (48/220), 10.9% (24/220), and 26.4% (58/220), respectively, in the entire study population. The frequency of G1 variants was significantly increased among those with ESKD at 55.0% (33/60) compared to non-ESKD HIV-positive and HIV-negative cohorts at 13.8% (11/80) and 17.5% (14/80), respectively (p < 0.001). The presence of both G1 risk genotypes (rs73885319 and rs60910145) was higher among those with ESKD at 20% (12/60) compared to the two control cohorts without ESKD at rates of 3.8% (3/80) and 1.3% (1/80), respectively (p < 0.001). In logistic regression, the presence of both G1 (OR,14.6; p ≤ 0.001) and G1/G2 (OR,11.9; p ≤ 0.001) risk genotypes were strong predictors of ESKD development.

Conclusion

The presence of G1:rs73885319 and rs60910145 polymorphisms of the APOL1 gene is suggested to be a significant factor in the development of ESKD.
#934 Mortality predictors in advanced chronic kidney disease patients on conservative kidney management: insights from a retrospective multicenter study
Authors: Trigo Filipa , Figueiredo Cátia , Farinha Ana , Cunha Teresa , Azevedo Ana , Santos Paulo
Published: May 2024

Background and Aims

In general, patients with advanced chronic kidney disease (ACKD) on dialysis have a better survival than patients on conservative kidney management (CKM). However, in elderly and frail individuals, with multiple comorbidities, the survival benefits of dialysis seem to be lost. Although the focus of CKM is not quantity but quality of life (QoL), it is important to identify survival modifiers and mortality predictors that may eventually influence QoL and the development of symptoms.

Method

An observational retrospective and multicenter study of ACKD patients on CKM was conducted from July/2015 to December/2023. Data was retrieved from electronic records, encompassing kidney function, analytical parameters, functional and fragility state, and symptoms evaluation (using Palliative Outcome Scale—Renal). The Kaplan-Meier curves and Cox proportional hazards multivariable regression were used for survival analysis and to evaluate 180-day mortality predictors.

Results

A total of 212 patients (56.6% females), with a mean age of 83 years old and a mean follow up time of 220 ± 239 days, were included. The follow-up time was determined by the end of the observational period or the patient's death. 56.1% died before a 180-day follow-up period. The main causes for the ACKD were multifactorial (29.7%) and indeterminate (25.9%). The majority (80.7%) had nephrologist oversight before a CKM team initiated its follow-up, and 63.6% opted for CKM as their first treatment choice.

Survival at 180 days (Fig. 1) differed significantly depending on sex (51.3 vs 65.6, p = 0.021), age under 80 years-old (51.3 vs 73.9, p = 0.000), provenance (0 vs 39.4 vs 83 vs 93.8, p = 0.000), albumin value (32.7 vs 65.5, p = 0.032), and symptoms such as anorexia and pain (53 vs 95.5, p = 0.000; and 54.5 vs 88.9, p = 0.000).

Regarding to mortality predictors (Table 1), albumin under 3g/dL, anorexia and pain were independent predictors of mortality.

Conclusion

Understanding factors associated with increased mortality and higher rates of survival in CKM patients is crucial to better manage this population. Pain, albumin <3g/dL and anorexia, which may reflect patients with worse nutritional status, were shown to be independent predictors of mortality. Therefore, controlling these symptoms, which often impair QoL, and improving nutritional status appears to have an impact not only on QoL but also on survival of ACKD patients on CKM.
#1983 In vitro iohexol adsorption in cartridges with mesoporous styrene-divinylbenzene sorbent
Authors: Lorenzin Anna , de Cal Massimo , Ramírez-Guerrero Gonzalo , Corradi Valentina , Reis Thiago , Marcello Matteo , Ronco Claudio , Zanella Monica
Published: May 2024

Background and Aims

Patients with pre-existing chronic kidney disease (CKD) present the highest risk of developing contrast-associated acute kidney injury (CA-AKI). Iodinated contrast agents such as iohexol (molecular weight 821 Da) don't bind to proteins and are easily removed by hemodialysis filters. However, the session time necessary to remove approximately 75% of the injected iohexol load is around six hours. Due to lack of evidence, current guidelines do not recommend to start hemodialysis in CKD patients in conservative management after the administration of iodinated contrast media to prevent or mitigate CA-AKI. Still, a strong rationale supports the removal of iodinated contrast media because of its nephrotoxicity. In this study, we aimed to investigate the capability of a mesoporous styrene-divinylbenzene sorbent to bind iohexol in vitro.

Method

We used 1,000 mL of saline solution spiked with 40 mL of iohexol 350 mg/mL in a closed-loop configuration. Iohexol concentration was 14 mg/mL. The amount of the iodinated radiocontrast was proportional to the amount used in complex percutaneous coronary interventions (worst-case scenario), around 200 mL, in a 70 kg person with an estimated blood volume of 5,000 mL. The solution circulated through a HA380 mini-module cartridge filled with 75g of mesoporous styrene-divinylbenzene sorbent beads at 250 ml/min.

The experiment was carried out twice with the same setup.

Samples were collected at eight-time points (0, 5, 10, 15, 20, 30, 40, and 60 minutes) from the reservoir to measure iohexol concentration. The analysis of the samples was carried out in duplicate. The removal ratio (RR) was calculated considering the initial concentration (C(0)) and the variation of the concentration during the experiment (C(t), where t is the time point), as follows:

$RR( \% ) = \frac{{C( 0 ) - C( t )}}{{C( 0 )}}100$

Results

In the first experiment, the removal ratios after 5, 30, and 60 minutes were 23.4%, 45.8%, and 52.9%, respectively on average. In the second experiment, the reduction ratios after 5, 30, and 60 minutes were 23.4%, 45.5%, and 53.1%, respectively on average. After 30 minutes, the adsorption curved plateaued, indicating cartridge saturation (Fig. 2).

Conclusion

This in vitro model demonstrated that HA380 sorbent cartridge was effective in removing iohexol. The use of hemoadsorption as a strategy to remove iodinated contrast media warrants further investigation because of its clinical potential to reduce the exposure to nephrotoxic contrast agents and CA-AKI.
#1449 Maturation of tertiary lymphoid structures in progressive kidney damage due to chronic phosphate load
Authors: Weingärtner Nina , Richter Beatrice , Walles Franziska , Kapanadze Tamar , Schmitz Jessica , Bräsen Jan Hinrich , Limbourg Florian , Haffner Dieter , Leifheit-Nestler Maren
Published: May 2024

Background and Aims

We have recently shown that a high phosphate diet (HPD) in mice leads to an increase in FGF23 levels and causes progressive tubular damage and interstitial fibrosis with increased accumulation of macrophages and concomitant perivascular immune cell aggregates in the corticomedullary zone. Such tertiary lymphoid structures (TLS) can develop as a result of chronic inflammation and have already been described in lupus nephritis and IgA nephropathy, among others. In our model, the question arose to what extent damage to the proximal tubule is temporally associated with the development and maturation of TLS and which factors favor TLS development.

Method

Wild-type mice were fed HPD for 1, 2, 3, 4 and 6 months and the kidneys of each were compared with those of mice on a normal phosphate diet (NPD). To evaluate the effect of high FGF23 ± phosphate, Fgf23 was overexpressed in mice on NPD and HPD using an adeno-associated virus (AAV-Fgf23), and hypophosphatemic Hyp mice were used.

Results

An increased tubular damage score was seen after only two months of HPD. In parallel, perivascular immune cell clusters developed in the corticomedullary zone and in the renal cortex, which were characterized by aggregates of CD45R+ B cells and CD3+ T cells, as well as LYVE1+ lymphatic vessels after three months of HPD and were accompanied by increased expression of venous markers (Plvap, Aplnr, EphB4) and cell adhesion molecules (Sell, Vcam1, Madcam1). Further analyses showed a time-dependent induction of the immunofibroblast-derived chemokines Cxcl13 and Ccl19, as well as the lymphotoxins Lta and Ltb, which are important for the differentiation of immunofibroblasts into follicular dendritic cells (FDC) and follicular reticular cells (FRC). Already after four months of HPD, proliferating B-cell clusters with FDCs, FRCs located in T-cell clusters, podoplanin+ networks, high endothelial venules, plasma cells and increased IgD synthesis indicated fully mature TLS, while tubular damage and fibrosis continued to increase until six months of HPD. Compared to AAV-Fgf23 mice on NPD, only AAV-Fgf23 animals on HPD developed tubular damage with fibrosis and fully mature TLS. Hypophosphatemic Hyp mice with high FGF23 showed neither signs of tubular damage nor the development of TLS.

Conclusion

The development of renal TLS due to chronic high phosphate load coincides with the development of tubular damage, with earlier maturation of TLS and progression of tubular damage.
#299 The association between body fat distribution, albuminuria, and mortality in relatively healthy adults
Authors: Claudel Sophie , Verma Ashish
Published: May 2024

Background and Aims

Albuminuria is a risk factor for kidney disease progression and cardiovascular disease (CVD). Metabolic syndrome has been associated with incident albuminuria. We aimed to understand which measures of adiposity are associated with albuminuria and mortality in relatively healthy adults.

Method

We included 8,215 adults in the National Health and Nutrition Examination Survey (years 2003-6 and 2011-2016) without prior CVD, estimated glomerular filtration rate <60 ml/min/1.73 m2 (eGFR), diabetes, hypertension, or prior dialysis. We used multivariable adjusted linear regression modelling to evaluate sex-stratified relationships between urine albumin excretion and multiple measures of adiposity, controlling for urine creatinine. We then performed sex-stratified multivariable adjusted Cox regression models of the association between adiposity and all-cause mortality. Measures of adiposity included android fat mass index (FMI), gynoid FMI, android-to-gynoid ratio, subcutaneous FMI, abdominal FMI, visceral FMI, body mass index (BMI), and waist circumference. Models were adjusted for age, race or ethnicity, education, food insecurity, health insurance, survey year, physical activity, eGFR, total cholesterol, systolic blood pressure, hemoglobin A1c, and urine albumin:creatinine ratio (UACR), and menopausal status (among women). Models were subsequently adjusted for BMI and waist circumference.

Results

The sample was 52.3% women, the mean (standard deviation, SD) BMI was 27.1 kg/m2 (SD 6.7), and the median UACR was 5.4 mg/g [3.8, 8.6]. Over a median follow up of 7.8 years [IQR 5.3-14.3], there were 128 deaths among men and 89 deaths among women. Among men, a 1-SD increase in android fat mass index (FMI) was associated with 13.1% (95% CI 4.5, 22.5) higher albuminuria. Similarly, a 1-SD increase in visceral FMI was associated with 8.3% (95% CI 1.3, 15.7) higher albuminuria. BMI was non-linearly associated with albuminuria among men. Among women, a 1-unit increase in android to gynoid ratio was associated with 47.7% lower albuminuria (% change = −47.7 (95% CI −61.4, −29.3). A 5 kg/m2 increase in BMI was associated with 11.0% lower albuminuria (% change = −11.0 (95% CI −15.0, −6.7) and a 3 cm increase in waist circumference was associated with 1.6% (95% CI 0.03, 3.0) higher albuminuria. Among men, a 1-SD increase in abdominal FMI was associated with 2.09-fold higher risk of all-cause mortality (HR 2.09 [95% CI 1.16-3.74]), independent of BMI and waist circumference. Among women, a 1-SD increase in gynoid FMI was associated with 56% decreased risk of all-cause mortality (HR 0.44 [95% CI 0.20-0.88]), independent of BMI and waist circumference.

Conclusion

Adiposity is differently associated with albuminuria and mortality in relatively healthy men and women. Sex-specific patterns of adipose deposition may inform CVD risk stratification.
#444 Novel MRI filtration fraction method to assess glomerular hemodynamics in diabetic kidney disease
Authors: Hockings Paul , Makvandi Kianoush , Unwin Robert John , Hulthe Johannes , Baid-Agrawal Seema
Published: May 2024

Background and Aims

Filtration fraction (FF) is the ratio of the glomerular filtration rate (GFR) to renal plasma flow (RPF) and is therefore an important measure of glomerular hemodynamics. The gold standard method to assess effective RPF is renal clearance of para-aminohippuric acid (PAH) but technical and labour-intensive difficulties limit its application [1]. Quicker and simpler assays of FF are needed, particularly to assess the renal hemodynamic dysfunction (hyper- or hypofiltration) and effects/mode of action of therapeutic interventions in chronic kidney disease (CKD). We assessed a novel magnetic resonance imaging (MRI) technique to measure FF in patients with diabetic kidney disease (DKD) and healthy controls (HC) [2].

Method

This cross-sectional sub-study included 32 DKD subjects with measured GFR (mGFR) ≤ 60 ml/ min/1.73 m2 and stratified into the following GFR stages as per the Kidney Disease Improving Global Outcomes (KDIGO) classification: stage G3a (mGFR 45-59 ml/ min/1.73 m2, n = 3), G3b (mGFR 30-44 ml/ min/1.73 m2, n = 8), G4 (mGFR 15-29 ml/ min/1.73 m2, n = 15), G5 (<15 ml/ min/1.73 m2, n = 6), and 18 age-, gender-matched HC with mGFR ≥ 60 ml/min/1.73 m2. All subjects were 18-79 years old. mGFR was assessed using iohexol clearance. Renal blood flow (RBF) (ml/min) was measured by a 5-minute add-on phase contrast MRI of the renal artery of each kidney and then summed together. RBF was corrected for Body Surface Area. RPF and FF were calculated as below:

${\rm{RPF }} = {\rm{ RBF}} \times \ ( {1\ -{\rm{ Hematocrit}}} )$

${\rm{FF}} = {\rm{mGFR}}/{\rm{RPF}}$

Results

RBF and mGFR were highly correlated (R2 = 0.70, Fig. 1). FF was 17.1% for HC and decreased with increasing degrees of renal impairment (Fig. 2). While the difference between HC and G3a DKD group was not significant, there was highly significant difference between HC and all other DKD groups (p < 0.001). The standard deviation in the G3a group was relatively large with only 3 subjects in this group.

Conclusion

The phase contrast MRI scan can provide a quick and simple measurement of glomerular hemodynamics and therewith further insights into the pathophysiology of DKD and its progression. Given the limitations of the existing method for assessing renal plasma flow, this MRI method can facilitate the inclusion of filtration fraction in DKD clinical trials. Further, the described method could be used to identify hyperfiltration, a compensatory mechanism that can influence results in clinical trials of DKD.
#1415 The association between social isolation and all-cause mortality in patients with chronic kidney disease: a prospective cohort study
Authors: Zeng Xiaoxi , Chunyang Li , Fu Ping
Published: May 2024

Background and Aims

Social isolation has been linked to several diseases and adverse outcomes, such as type 2 diabetes and cardiovascular events. The current study aimed to evaluate the association between social isolation and all-cause mortality in patients with chronic kidney disease (CKD).

Method

From the UK Biobank, a population-based cohort study, we included 16,250 participants that were diagnosed with CKD and with decreased estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2) at baseline. Participants were classified as socially isolated if they met at least two of the following criteria: (1) living alone; (2) having close contact with others less than once per month; or (3) lacking leisure or social activities involving interpersonal interaction. The outcome was all-cause mortality obtained from death registries. We performed Cox proportional hazards model to estimate the hazard ratio of social isolation for all-cause death in CKD patients.

Results

Over a median follow-up of 13.5 years (interquartile range (IQR): 12.6-14.4 years), 3,498 deaths were recorded. The all-cause mortality was 21.5% in the whole cohort, and 20.2%, 55.3% and 62.4% in CKD stage 3, stage 4 and stage 5 respectively. A total of 11.1% of participants were considered to be socially isolated. The results showed that social isolation was independently associated with increased risk for all-cause mortality when compared with no isolation (HR 1.22, 95% CI 1.11 to 1.34) (Fig. 1), after adjusting for age, sex, Townsend deprivation index, education levels, income levels, BMI, smoking status, diet habit, status of physical activity, consumption of alcohol, hypertension, diabetes, Charlson comorbidity index and CKD stages. Subgroup analyses showed that the significant association was only observed in men (HR 1.28, 95% CI 1.14 to 1.45) and in patients with CKD stage 3 (HR 1.23, 95% CI 1.11 to 1.36), but not in women or in those with more advanced renal failure (Fig. 1).

Conclusion

Social isolation was independently associated with a higher hazard of all-cause mortality in patients with CKD. The association was more significant in men and in patients with mildly decreased renal function.
#2489 The prevalence of chronic kidney disease in different altitude areas: results from the China multi-ethnic cohort study
Authors: Wang Yujiao , CI Linongbu , Zhao Xing , Zeng Xiaoxi
Published: May 2024

Background and Aims

Chronic Kidney Disease (CKD) poses a significant public health challenge with substantial implications for human well-being. In China, there are significant geographical differences in the prevalence of CKD, with the highest prevalence in the southwest region, which may be related to differences in geographical environment and lifestyle. This study aimed to investigate variances in the prevalence of CKD across different altitude areas in southwest China.

Method

In this cross-sectional study, we used data from the China Multi-Ethnic Cohort (CMEC). CMEC was established in five provinces of Southwest China and recruited a total of 99,556 participants between 2018 and 2019. Altitude information for each participant was extracted from the Shuttle Radar Topography Mission (SRTM) (version 4) data based on their residential address. To facilitate analysis, we categorized them into groups of low altitude (0-1499 m) and high altitude (≥1500 m). CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Crude and age-standardized prevalence of CKD was calculated by using R.

Results

A total of 92,163 participants were included in the study, and 39.7% were men. Among the current cohort, 30,904 were high-altitude residents, and 61,259 were from low altitude. Among the participants, 1636 cases of CKD were identified, corresponding to a prevalence of 1.78%. We found, the prevalence of CKD in high altitude group was higher than that in low altitude group, and the former is 2.53%, the latter is 1.40%. The age-standardized prevalence were 1.35% and 2.73% for the low and high altitude groups, respectively, and 1.38% and 2.57% for the sex-standardized groups.

Conclusion

In southwestern China, the prevalence of CKD was higher in the high altitude group than the low altitude group. And after adjusting for age and gender, the prevalence of CKD remained lower in the low-altitude group, and the gap slightly increased.
#2590 Electrolyte abnormalities in HIV patients with CKD
Authors: Lahoti Abhishek , Saha Rajdeb , Attur Ravindra Prabhu , Nagaraju Shankar Prasad , Rangaswamy Dharshan , Rao Indu Ramachandra , Shenoy Srinivas Vinayak , Bhojaraja Mohan V
Published: May 2024

Background and Aims

Individuals with HIV infection and CKD are prone to various water & electrolyte disorders with previous studies showing prevalence of 70%. Many of these disturbances remain clinically silent until they reach an advanced stage, emphasizing the need for a high level of clinical suspicion and awareness, as they contribute to both morbidity and mortality. The prevalence of CKD in HIV patients has been increasing, yet data on electrolyte disturbances is sparse. The study we conducted aims to determine electrolyte imbalances in this population.

Method

Prospective observational single center study for a period of 2 years including HIV seropositive patients >18 years of age who were screened for CKD as per KDIGO definition (eGFR < 60 ml/min/1.73 m2 or significant proteinuria > 300 mg/day for more than 3 months). Demographic features, laboratory investigations for serum electrolytes including Sodium, Potassium, Phosphorous & Calcium levels were done at baseline with follow up at 3, 6 & 12 months.

Results

Out of 695 HIV patients screened, 56 who had CKD were included in our study. The average age was 53.8 ± 11.3 years, including 41 males (73.2%). Median creatinine at baseline was 1 (1.3) mg/dL, & median eGFR was 59 (24.82) ml/min/1.73 m2 (Table 1). Commonest abnormality at baseline was hyponatremia (53.6%), and only 8.9% had severe hyponatremia (<125 mmol/L). Other abnormalities prevalent were hypocalcemia (35.7%) and hypophosphatemia (46.4%). Follow up details are presented in Table 2.

Conclusion

CKD was prevalent in 56 (8%) of our patients. Dyselectrolytemias were seen in 91% of study population. Hyponatremia (89.2%) was the commonest electrolyte imbalance followed by Hypophosphatemia (62.5%) & Hypocalcemia (57.1%). Notably, our study identified a significantly higher incidence of hypocalcemia, and hypophosphatemia compared to other studies.
#2661 High albuminuria in CKD: prevalence and characteristics in a real-world clinical setting
Authors: Svensson Maria K , Bodegard Johan , Thuresson Marcus , Ambery Philip
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) is estimated to affect 1 in 10 adults globally. CKD is associated with increased morbidity, mortality and decreased quality of life, and places a financial burden on the healthcare system. Furthermore, persistently high albuminuria is associated with an especially high risk of renal and cardiovascular complications in patients with CKD. With recent advances in therapeutic approaches for CKD management, both with sodium–glucose co-transporter-2 inhibitors (SGLT2i) and endothelin receptor antagonists as add-on to renin–angiotensin system blockade, it is important to highlight patients with persistent urine albumin-creatinine ratio (UACR; ≥700 mg/g). In patients with UACR >700 mg/g, a novel and highly selective endothelin receptor A antagonist (zibotentan) plus the SGLT2i dapagliflozin significantly reduced albuminuria versus dapagliflozin plus placebo (ZENITH-CKD trial). Hence, it is important to understand the prevalence and characteristics of patients with CKD and high albuminuria in a real-world clinical setting.

Methods

We used a large USA claims database (Optum's de-identified Clinformatics® Data Mart Database [CDM]) to identify patients aged ≥18 years with a CKD diagnosis and a UACR measurement ≥200 mg/g. Patients were indexed on 1st January 2022 and grouped into two UACR groups: ≥700UACR group (≥700 mg/g) and <700UACR group (200–699 mg/g). Continuous variables were calculated as medians with interquartile range (IQR). Baseline characteristics and comorbidities included age, sex, median UACR, median estimated glomerular filtration rate (eGFR) and a history of heart failure.

Results

Of 53,306 patients with CKD and UACR ≥200 mg/g, 22,504 (42%) were in the ≥700UACR group and 30,802 (58%) in the <700UACR group (Fig. 1). Patients were more frequently men in both groups (57%). Median UACR was 1459 mg/g (IQR 977–2473) in the ≥700UACR group and 341 mg/g (IQR 256–474) in the <700UACR group. Patients in the ≥700UACR group were slightly younger (72 vs 74 years), had a higher frequency of heart failure (42% vs 34%) and lower eGFR (37 mL/min/1.73 m2 [IQR 21–55] vs 49 mL/min/1.73 m2 [IQR 34–67]) compared to the <700UACR group.

Conclusions

In this contemporary study of patients with albuminuric CKD, more than 4 out of 10 had UACR levels ≥700 mg/g. These patients were slightly younger, had more severe CKD, and greater prevalence of cardiorenal disease compared to those with UACR 200–699 mg/g. Patients with UACR levels ≥700 mg/g have an urgent need for improved risk management.
#3104 Adequacy of nephroprotective prescription in an elderly diabetic population in a primary care setting
Authors: Queiros Ana Rita , Figueiredo Rafael , Fonseca Clara
Published: May 2024

Background and Aims

The prevalence of chronic kidney disease (CKD) has been increasing and one of the main risk factors is diabetes mellitus (DM). The addition of sodium-glucose cotransporter 2 inhibitors (SGLT2i) to the renin-angiotensin inhibitors (RASi) is recommended in patients with DM and CKD due to the benefits in metabolic control, decrease in proteinuria, and in delaying glomerular filtration decline.

Method

A retrospective cohort was performed and included a sample of patients with diabetes registered and monitored in a primary care facility. A random sample was selected, calculated for an expected prevalence of 40%, error of 4%, and alpha of 0.05. The primary outcome was to assess the adequacy of nephroprotective prescription. Secondary outcomes were to determine the prevalence of CKD (and associated factors) in the sample, and to assess the percentage of patients with correct CKD diagnosis. Demographic and analytical data of patients (glomerular filtration rates and values of albuminuria) were collected from their electronic health records. Statistical analysis was performed using SPSS v28.0. A p-value < 0.05 was considered statistically significant. The study protocol was approved by the Ethics Committee.

Results

338 patients were included, 58% were men, and with a mean age of 71.4 years. 22.2% [95% CI 16.2-29.7%] of patients had the pathology properly coded in the problem list. The prevalence of CKD found was 42.6% [95% CI 37.4-48.0%]. Most patients were in stages G2 (33.3%), G3a (30.6%) and G3b (14.6%). Concerning albuminuria, most were in stage A2 (68.8%). Of the patients with CKD, 77.1% [95% CI 69.6%-83.2%], 60.4% [95% CI 52.3%-68.0%] and 43.1 [95% CI 35.3–51.2%] were medicated with RASi, SGLT2i and both, respectively.

Conclusion

In this primary setting study, the majority of this elderly population was under nephroprotective therapies (RASi and/or SGLT2i). The relatively low coding suggests underdiagnosis. Further optimization of nephroprotective therapies can be made in order to avoid renal failure, as long as the pathology is properly recognized.
#989 Fund and incentivize multidisciplinary CKD care: what can we learn from the French CKD bundled payment program?
Authors: Raffray Maxime , Vigneau Cécile , Couchoud Cécile , Augé Estelle , Bricard Damien , Raynaud Denis , Campéon Arnaud , Frimat Luc , Bayat Sahar
Published: May 2024

Background and Aims

Multidisciplinary care (MDC) is crucial to slow down the progression of Chronic Kidney Disease (CKD) and prevent or post-pone kidney replacement therapy. To incentivize the development of that care, France launched a nationwide bundled payment program (CKD-BP) targeted to patients with CKD G4 and G5. In this study, we review the implementation of the program, 3 years into its launch.

Method

First, using the CKD-BP program data collected by participating facilities, we described the characteristics and trajectories of patients enrolled from 2020 through 2022. Second, from exploratory interviews with medical and management staff, we performed a thematic analysis to identify the obstacles encountered during implementation and the changes introduced by the program.

Results

Since 2020, 157,863 patients were reported by 408 facilities (median age 75 y-o, 40% women, 77% G4). Missing data frequencies were high for comorbidities. Each year, around 4200 dialysis start (5% of patients) and 2600 deaths (3% of patients) were reported. On average, 47% and 40% of patients visited nurses and dietitians at least once a year respectively. From 22 interviews across 7 facilities, we identified challenges of implementation: adapting information systems, gathering the support of facility management and organizing the care in a context of workforce shortage, specifically nurses. Despite those challenges, facilities welcomed positively the new model, notably with increased time between nurses and patients and affirmation of dietitian's role.

Conclusion

We estimate the exhaustiveness of the CKD-BP program at 40% of all French patients with G5 CKD (around 4,600 dialysis start reported in 2021, compared to 11,000 from the national exhaustive REIN registry data). The results of this study suggest that interventions to accompany facilities in adapting their information systems are a priority to ensure efficient allocation of medical time and quality of the data. The results also suggest the need for increased flexibility regarding what professional is considered in the CKD-BP program, beyond nurses and dietitians. These challenges remain to be addressed in order to complete a successful shift from fee-for-service to assessable value-based care for CKD in France.
#832 Sickle cell trait and APOL1 high risk genotype increase the risk of ESKD similar to diabetes in British Africans
Authors: Gilchrist Mark , Sharp Luke , Murray-Leech Jacques , Patel Kashyap
Published: May 2024

Background and Aims

Little is known of the risk of end-stage kidney disease (ESKD) in British Africans with Sickle Cell Trait or APOL1 High-risk genotypes. We aim to determine the prevalence of the APOL1 high-risk genotype and genetically defined Sickle Cell Trait in British Africans and their association with ESKD.

Method

We analysed 7380 British Africans from a UK population cohort, UK Biobank. It contains deep phenotypes, biomarkers, and DNA sequence data. We used whole exome sequencing data to identify carriers of known APOL1 high risk genotypes (G1G1, G1G2, G2G2) and SCT (heterozygous carriers of p.Glu7Lys in HBB). We identified individuals with ESKD (in receipt of renal replacement therapy including kidney transplant) using self-report, hospital admissions records, and general practice records. We used a cox proportional hazard model to determine the risk of ESKD with these genotypes adjusted for age, sex, hypertension, smoking and diabetes.

Results

1131/7380 (17.9%) British Africans carry the APOL1 High risk genotype whereas 860/7380 (14.3%) had genetically defined SCT. Both risk states were found in 216/7380 individuals. Together, 32.2% carry one or both of these variants and 36/2207 (1.6%) developed ESKD. Of those with neither SCT nor APOL1 HR genotype 32/5173 (0.67%) developed ESKD.

The multivariable cox-proportional hazard model showed that APOL1 high risk genotype increased the risk of ESKD by two-fold (HR 2.12-95% CI 1.19-3.79), p = 0.011. Surprisingly, the risk of ESKD was also two-fold higher in SCT carriers (HR 2.59 95% CI 1.44-4.68), p = 0.002 independent of APOL1 genotype. This risk was of ESKD for people with either SCT or the APOL1 high risk genotype was similar to that associated with diabetes (HR 2.75 95% 1.58-4.80), p < 0.001.

The polygenic score for eGFR did not change the risk of ESKD in these carriers.

Conclusion

We show for the first time that 1 in 3 British Africans carry either two APOL1 high-risk variants or sickle cell trait, both of which double the risk of ESKD. These genetic risk factors increase the risk of developing ESKD to a level similar to that resulting from diabetes. A sensible starting point would be a trial of screening and aggressive management of conventional risk factors for ESKD.
#2888 Measured glomerular filtration rate and risk of adverse outcomes in 6059 patients from the Stockholm CREAtinine Measurements (SCREAM) project
Authors: Fu Edouard L , Coresh Josef , Grams Morgan , Inker Lesley , Levey Andrew , Carrero Juan-Jesus
Published: May 2024

Background and Aims

Evidence on the risks of adverse outcomes associated with glomerular filtration rate (GFR) has been limited to estimated GFR (eGFR), due to limited availability of large-scale data with measured GFR (mGFR). These studies either used creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys), which can be influenced by the non-GFR determinants of creatinine and cystatin C. Here, we aimed to (1) quantify associations between mGFR and the risk of all-cause mortality and kidney failure with replacement therapy (KFRT) and (2) investigate which filtration marker most closely resembled these associations.

Method

We included 6059 adults referred for single-point plasma iohexol clearance between 2011-2021 in Stockholm, Sweden (SCREAM project), and who had simultaneous measures of creatinine and cystatin C. eGFR was calculated with the CKD-EPI 2012 (eGFRcys) and 2021 (eGFRcr and eGFRcr-cys) equations. Hazard ratios were estimated using Cox regression, adjusting for age, sex, medical history, medications and urinary albumin-to-creatinine ratio (UACR).

Results

Mean age was 59 years, 40% were women, median mGFR was 66 ml/min/1.73 m2 and median UACR was 1.1 mg/mmol. During median 3.8 years of follow-up, 1961 individuals died and 425 progressed to KFRT. Associations between mGFR and mortality increased linearly for values <90 ml/min/1.73 m2 and were not statistically significant between 90-120 ml/min/1.73 m2 (Figure). Compared with mGFR of 90 ml/min/1.73 m2, hazard ratios for mortality were 1.5 (95% CI 1.3-1.6), 1.7 (1.5-1.8), 2.0 (1.8-2.1) and 2.4 (2.0-2.7) for 60, 45, 30 and 15 ml/min/1.732, respectively (Table). eGFRcr-cys most closely resembled the mortality risk relationships of mGFR. Conversely, eGFRcr had a strong U-shaped pattern with underestimation of risks <90 ml/min/1.73 m2 and overestimation of risks between 90-120 ml/min/1.73 m2; for eGFRcys this pattern was reversed. Associations between mGFR and KFRT were also linear (Figure). Compared with mGFR of 60 ml/min/1.73 m2, hazard ratios for KFRT were 2.1 (1.4-3.0), 6.2 (4.5-8.5), and 32.1 (23.4-44.0) for 45, 30 and 15 ml/min/1.732, respectively (Table). Both mGFR and estimating equations displayed similar monotonic risk associations.

Conclusion

In the largest study on mGFR and outcomes to date, lower mGFR was linearly associated with an increase in the risks of mortality and KFRT. eGFRcr-cys closely resembled the relationship between mGFR and mortality, whereas eGFRcr under-estimated mortality risk and had a U-shaped association. All estimating equations had similar associations with KFRT risk.
#2033 Patient characteristics and outcomes of an inter- and multidisciplinary nephrology and cardiology clinic
Authors: Rho Elena , Martinetti Christian , George Britta , Ruschitzka Frank , Frank Michelle , Schachtner Thomas
Published: May 2024

Background and Aims

The prevalence of cardiorenal syndrome is increasing due to the growing number of patients with chronic kidney disease (CKD) and heart failure (HF). To further improve outcomes in this high risk population, an interdisciplinary, evidence-based and patient-centered approach is advocated. Hence, it was the aim of this study to identify and describe the patient population which might profit from an inter- and multidisciplinary nephrology and cardiology clinic at a tertiary university hospital.

Method

We screened 552 patients who from 01.01.2015 and 30.06.2022 had been in the nephrology and in the cardiology outpatient clinics of the University Hospital of Zurich. Patients with kidney or heart transplantation or on dialysis were excluded. Out of the remaining patients, we identified 223 patients having CKD 2-5 and HF. Characteristics with respect to entity and cause of kidney and heart disease, cardiovascular risk factors, therapy, incidence of acute kidney injury (AKI), hospitalisations and patient survival were recorded.

Results

The most common cause of CKD was a cardiorenal syndrome type 2 (42%, 95/223). 59/223 (26%) had at least moderate albuminuria. At the beginning of follow-up, 61/223 (26%) were in CKD2, 95/223 (42%) in CKD3a, 47/223 (21%) in CKD3b, 6/223 (7%) in CKD4 1, 2/223 (1%) in CKD5. Ischemic cardiomyopathy was the most common cause of heart failure, (36%, 80/223 patients). 119/223 patients (53%) had HFrEF, 41/223 (19%) HFmrEF and 63/223 (28%) HFpE. 64/223 (28%) of the patients were treated with SGLT2i,159/223 (71%) with RASi of which 37 (17%) were on an ARNI. Patients under combined RASi and SGLT2i were younger (66 vs 73 years, p = 0.005), were more likely to have diabetes (44% vs 30%), HFrEF rather than HFpEF (70% vs 7% p = 0.002) and had a better kidney function at the beginning of follow-up (eGFR 65 vs 55 ml/min/1.73 m2, p < 0.001).

Hospitalization-rate due to HF and incidence of AKI were high with 0.6/patient/year and 4.8/patient/year respectively. 72/223 (32%) patients died during the mean follow-up of 3.1 years.

Conclusion

We identified a high-risk patient population with cardiorenal disease that might particularly benefit from evidence-based and patient-centered interdisciplinary care. A cardiorenal outpatient clinic may have the potential to improve a personalized approach in more vulnerable patients.
#2079 The impact of body composition measures on survival and cardiovascular events in patients with chronic kidney disease
Authors: Randhay Ashveer , Horner Daniela Viramontes , Fluck Richard , Taal Maarten W , Eldehni Tarek
Published: May 2024

Background and Aims

Multimorbidity, frailty and sarcopenia are increasingly prevalent in people with chronic kidney disease (CKD). Creatinine Muscle Index (CMI) has been proposed as a novel surrogate marker of muscle mass, and lower CMI was associated with frailty and increased mortality in the Atherosclerosis Risk in Community Study [1]. Waist to hip ratio (WHR) has also been proposed as a surrogate marker of visceral adiposity. In order to investigate the impact of body composition on outcomes, we analysed data collected from a large CKD cohort using CMI and WHR as markers of muscle mass and adiposity respectively to examine their effects on 5-year survival and cardiovascular events.

Method

1741 people with CKD stage 3 were recruited from 32 primary care practices. Cystatin C was measured using the Abbott c16000 Analyser (Abbott Diagnostics). eGFR cystatin (eGFRcys) was calculated using the CKD-EPI Cystatin C Equation (2012). CMI was calculated as the product of serum creatinine and eGFRcys (CMI [mg/day per 1.73 m2]= eGFRcys [ml/min per 1.73 m2] × serum creatinine [mg/dl] × 1 dl/100 ml × 1440 min/day). Cox proportional hazard model was used to examine if CMI and WHR predicted death or cardiovascular events.

Results

Mean age of the participants was 72.9 ± 9 years. Mean eGFRCr was 53.5 ± 11.8 ml/min/1.73 m2. Mean eGFRcys was 45.1 ± 16.0 ml/min/1.73 m2. Mean CMI was 766.45 ± 239.2 mg/day/1.73 m2. 300 (17.2%) participants died during 5 years of observation.

In a Cox proportional hazards model which included CMI, WHR and age, lower CMI per standard deviation change (B = −0.202, HR 0.817, p = 0.007), higher WHR per standard deviation change (B = 0.313, HR 1.37, p < 0.001) and age at baseline (B = 0.088, HR 1.09, p < 0.001) were independent predictors of mortality at year 5 of follow-up. CMI per standard deviation change also predicted cardiovascular events at 5 years using a univariable cox proportional hazards model, (B = −0.095, HR 0.91, p = 0.03).

Conclusion

Lower CMI (a surrogate measure of muscle mass) and higher WHR (a surrogate for visceral adiposity) independently predicted 5 year mortality and cardiovascular events in this predominantly elderly population with CKD stage 3. We conclude that body composition has an important impact on mortality and cardiovascular events in patients with CKD and the mechanisms of this merits further investigation. This could inform future interventions that reduce visceral adiposity and improve muscle mass in people with CKD.