bluuebunny/crossref_metadata_2025 huggingface dataset:
#3682 THE KETONE BODY BETA-HYDROXYBUTYRATE IS ASSOCIATED WITH BETTER KIDNEY FUNCTION OUTCOME IN PATIENTS WITH ADPKD: RESULTS OF THE DIPAK COHORT
Authors: Knol Martine , Bais Thomas , Geertsema Paul , Connelly Margery A , Bakker Stephan J L , Gansevoort Ron T , Van Gastel Maatje
Published: June 2023

Background and Aims

A dysregulated energy metabolism is a key feature of Autosomal Dominant Polycystic Kidney Disease (ADPKD), characterized by cystic cells being dependent on glucose and poorly able to use other energy sources such as ketone bodies. Besides providing energy, ketone bodies, especially beta-hydroxybutyrate, can act as signaling metabolites and reduce inflammation and oxidative stress. In experimental studies, raising ketone body concentration reduced disease progression. Therefore, we hypothesized that higher endogenous serum beta-hydroxybutyrate concentration reduces disease progression in patients with ADPKD.

Method

We analyzed data from the DIPAK cohort, a prospective observational cohort study that included 670 patients with ADPKD. Beta-hydroxybutyrate was measured at baseline using nuclear magnetic resonance spectroscopy. We excluded participants with type 2 diabetes, who used disease-modifying drugs (e.g., tolvaptan, somatostatin analogs), were not fasting, or had missing beta-hydroxybutyrate, leaving 521 participants for the analyses. Linear regression analyses were used to study cross-sectional associations and linear mixed-effect modeling for longitudinal associations.

Results

The median concentration of beta-hydroxybutyrate was 94 (IQR 68–147) μmol/L. Of the participants, 61% were female, the mean age was 47.3 ± 11.8 years, and the mean estimated glomerular filtration rate (eGFR) was 63.3 ± 28.9 mL/min/1.73 m2. Cross-sectionally, beta-hydroxybutyrate was neither associated with eGFR nor with kidney volume. Longitudinally, beta-hydroxybutyrate was positively associated with the eGFR slope (B = 0.37 (95% CI 0.11 to 0.62), p = 0.005) but not with kidney growth. After adjustment for potential confounders, every doubling in beta-hydroxybutyrate concentration reduced the annual rate of eGFR loss by 0.34 (95% CI 0.10 to 0.58, p = 0.005) ml/min/1.73 m2.

Conclusion

These analyses support the hypothesis that raising the beta-hydroxybutyrate concentration, one of the ketone bodies, reduces the rate of kidney function decline in patients with ADPKD.
#3769 MECHANOSENSITIVE ION CHANNEL PIEZO1 MEDIATES BLOOD PRESSURE HOMEOSTASIS BY REGULATING RENIN EXPRESSION IN MICE
Authors: Yang Xiaoqiang , Wang Le , Zeng Honghui , Luo Siweier , Zhou Yiming
Published: June 2023

Background and Aims

The renin-angiotensin system (RAS) plays a crucial role in the maintenance of fluid-electrolyte and blood pressure homeostasis. Renin, the step-limiting protease of the RAS, is produced, stored, and secreted by the renal juxtaglomerular (JG) cells, which are closely regulated by the blood pressure. Studies have shown that local blood flow-associated shear stress play an important role in renin expression and secretion. To date, however, the molecular identity through which JG cells respond to the blood pressure remains unclear.

Method

In this study, we determined the expression and subcellular localization of Piezo1 in JG cells by qPCR, Western blot, Immunofluorescence (IF), and multiplex immunohistochemistry. Then, a Fluo-4 AM-based calcium-imaging system was used to detect the dynamic changes of intracellular calcium in response to Piezo1 specific agonist Yoda1 and mechanical stress (MS)-induced by perfusion. Next, CRISPR/Cas9 technology was used to generate Piezo1 knockout JG cells to further confirm its contribution. Then, we used RNA-seq experiment to investigate the downstream signaling of Piezo1 in JG cells. Finally, we generated adeno-associated virus (AAV)-mediated kidney-specific Piezo1 knockdown mice to investigate the in vivo effect of Piezo1.

Results

We found that the mechanosensitive ion channel Piezo1 was co-expressed with renin in JG cells in mouse kidney slides as well as As4.1 cells, a commonly used JG cell line. Activation of Piezo1 by its agonist Yoda1 induced an intracellular calcium increase and reduced the expression of renin in these cells, while knockout of Piezo1 in JG cells abolished the effect of Yoda1. Meanwhile, fluid induced mechanical stress also led to an intracellular calcium increase and renin downregulation in wildtype but not Piezo1 knockout JG cells. Mechanistically, we demonstrated that activation of Piezo1 upregulated the Ptgs2 expression via the calcineurin-NFAT pathway and increased the production of Ptgs2 downstream molecule COX-2 and PGE2 in JG cells, which inhibited cAMP production and reduced renin expression in JG cells. In mice, we demonstrated that activation of Piezo1 significantly downregulated the blood pressure in wildtype but not kidney-specific Piezo1 knockdown mice.

Conclusion

In summary, these results revealed that activation of Piezo1 could lead to downregulation of the renin expression in vitro and in vivo, subsequently reduction of blood pressure, highlighting its therapeutic potential as a drug target of the renin-angiotensin system.
#4126 LONG-TERM VISIT TO VISIT VARIABILITY IN HBA1C AND KIDNEY RELATED OUTCOMES IN PERSONS WITH DIABETES
Authors: Xu Yang , Dong Shujie , Fu Edouard L , SjÖlander Arvid , Grams Morgan E , Selvin Elizabeth , Carrero Juan Jesus
Published: June 2023

Background and Aims

Glycated hemoglobin (HbA1c) is central to the routine monitoring of glycemic control in persons with diabetes, and poor glycemic control is an established contributor to the occurrence and progression of CKD, but whether long-term visit-to-visit variability in glycemic control predicts kidney outcomes is not well studied.

Method

We included all adults with type 1 or type 2 diabetes in Stockholm, Sweden, during 2006–2019, who had at least one annual outpatient HbA1c test in three consecutive years. We evaluated associations between baseline and time-varying HbA1c variability score (HVS, the percentage of total HbA1c measures that vary by >0.5% [5.5 mmol/mol] during a 3-year window), with the risk of CKD progression (composite of >30% eGFR decline and kidney failure), acute kidney injury (AKI, by clinical diagnosis or increase in creatinine ≥0.3 mg/dL over 48 h or 1.5 times creatinine over 7 days), and worsening of albuminuria.

Results

We included 93,598 adults with diabetes undergoing 891,536 routine HbA1c tests (median 8 tests per person) during a median follow-up of 5.2 years. Compared with persons showing low HbA1c variability (HVS 0–20%), any increase in variability was associated with a higher risk of adverse kidney outcomes. For example, for patients with a baseline HbA1c variability of 81–100%, the adjusted HR was 1.47 (95% CI, 1.38-1.56) for CKD progression, 1.27 [1.19-1.36] for AKI, and 1.28 [1.21-1.36] for worsening of albuminuria. Results were robust across subgroups (diabetes subtypes, baseline eGFR or albuminuria categories) and in sensitivity analyses including time-weighted average HbA1c or alternative metrics of variability.

Conclusion

A higher long-term visit-to-visit HbA1c variability is robustly associated with the risks of CKD progression, AKI and worsening of albuminuria.
#4917 AN EXOME-WIDE STUDY OF RENAL OPERATIONAL TOLERANCE
Authors: Massart Annick , Danger Richard , Olsen Catharina , Emond Mary , Viklicky Ondrej , Jacquemin Valérie , Soblet Julie , Duerinckx Sarah , Croes Didier , Perazzolo Camille , Hruba Petra , Daneels Dorien , Caljon Ben , Sever Mehmet Sukru , Pascual Julio , Pirson Isabelle , Ghisdal Lidia , Smits Guillaume , Giral Magali , Abramowicz Daniel , Abramowicz Marc , Brouard Sophie
Published: June 2023

Background and Aims

Renal operational tolerance is a rare and beneficial state of prolonged renal allograft function in the absence of immunosuppression. The underlying mechanisms are unknown. We hypothesized that tolerance might be driven by inherited protein coding genetic variants with large effect, at least in some patients.

Method

We set up a European survey of over 218,000 renal transplant recipients and collected DNAs from 40 recipients of an allogeneic kidney transplant who maintained good graft function (serum creatinine <1.7 mg/dL and proteinuria ≤1g/day or /g creatinine) in the absence of immunosuppression for at least one year. We performed an exome-wide association study comparing the distribution of moderate to high impact variants in 36 tolerant patients, selected for genetic homogeneity using principal component analysis, and 192 controls, using an optimal sequence-kernel association test adjusted for small samples.

Results

We identified rare variants (allele frequency < 1%) of HOMER2 (3/36, FDR 0.0387), IQCH (5/36, FDR 0.0362), and LCN2 (3/36, FDR 0.102) in 10 tolerant patients vs 0 controls. One patient carried a variant in both HOMER2 and LCN2. Furthermore, the three genes showed an identical variant in two patients each. The three genes are expressed at the primary cilium (p0= 0.01), a key structure in immune responses. Both LCN2 variants were located 9 base pairs apart, in the 20 amino-acid long signal peptide of the encoded NGAL protein, suggesting the possibility of a shared functional effect

Conclusion

Rare protein coding variants in a small set of primary cilium genes are associated with operational tolerance in a sizable portion of patients. Our findings have important implications for a better understanding of immune tolerance in transplantation and other fields of medicine.

ClinicalTrials.gov Identifier NCT05124444.
#4958 IMPROVEMENT OF NUTRITIONAL STATUS AFTER PARATHYROIDECTOMY IN PATIENTS RECEIVING MAINTENANCE HEMODIALYSIS
Authors: Disthabanchong Sinee , Saeseow Sarunya , Khunapornphairote Sirote , Suvikapakornkul Ronnarat
Published: June 2023

Background and Aims

Improvement in quality of life and survival have been reported after parathyroidectomy in patients with end-stage kidney disease. In addition to bone loss, protein-energy wasting has also been linked to excess parathyroid hormone (PTH) level. The present study examined the changes of nutritional parameters after parathyroidectomy in patients receiving maintenance hemodialysis compared non-parathyroidectomized patients.

Method

One hundred eighty-seven hemodialysis patients who underwent parathyroidectomy during 2012–2018 were identified (PTX group) and matched 1:1 to 479 patients with parathyroid hormone (PTH) levels ≤1000 pg/mL (non-PTX control group) and 187 patients with PTH levels >1000 pg/mL (pre-PTX control group) by propensity score. The matchings yielded 120 matched pairs from PTX and non-PTX groups (cohort 1) and 76 matched pairs from PTX and pre-PTX groups (cohort 2). Baseline and follow-up nutritional data were compared over the 12-month study period.

Results

In cohort 1, substantially lower serum albumin and creatinine/body surface area (Cr/BSA) and higher proportions of patients with serum albumin ≤38 g/L (low serum albumin) and Cr/BSA ≤380 μmol/L/m2 (low serum Cr/BSA) were observed in the PTX group. These parameters and the percentage of patients with total lymphocyte count <800 cells/mm3 (low TLC) improved substantially after parathyroidectomy. At follow-up, serum albumin, Cr/BSA and proportions of patients with low serum albumin and Cr/BSA became comparable to the non-PTX control group. The percentage of patients with low TLC was also lower at follow-up in the PTX group. Mixed-models analysis confirmed significant differences in the changes of serum albumin, Cr/BSA, proportions of patients with low serum albumin and TLC between the two groups. In cohort 2, there was no significant difference in baseline nutritional parameters. At follow-up, serum Cr/BSA was higher and proportions of patients with body mass index (BMI) ≤18.5 kg/m2, low TLC and low Cr/BSA were lower in the PTX group. Weight gain was more frequent and of greater magnitude in the PTX group in both cohorts. Higher baseline PTH level, parathyroidectomy and lower baseline serum albumin and creatinine were significantly associated with ≥10% increase in the BMI.

Conclusion

Parathyroidectomy was associated with nutritional improvement in maintenance hemodialysis patients with severe hyperparathyroidism.
#5499 COULD MESANGIAL C3 DEPOSITION BE AN INDEPENDENT PROGNOSTIC MARKER IN IMMUNOGLOBULIN A NEPHROPATHY?
Authors: Cetinkaya Hakki , Gursu Meltem , Yazici Halil , Cebeci Egemen , Eren Necmi , Altiparmak Mehmet Riza , Akcay Omer Faruk , Sahin Gulizar Manga , Basturk Taner , Atilgan Kadir Gokhan , Aydemir Nihal , Turgutalp Kenan , Dheir Hamad , Yılmaz MÜrvet , Sirali Semahat Karahisar , Tatar Erhan , Boz Saide Elif Gullulu , Mirioglu Safak , Kazan Sinan , Aydin Emre , Aydin Zeki , Turkmen Kultigin , Kutlay Sim , Karagoz Ferdi , Ogutmen Melike Betul , Ozturk Savas , Ozkan Oktay , Yıldız Nuriye , Dincer Mevlut Tamer , Yasar Emre , Gok Mahmut , Turkmen Aydin , Dede Fatih , Derici Ulver
Published: June 2023

Background and Aims

Immunoglobulin A nephropathy (IgAN) is a common primary glomerulonephropathy and the role of complement activation in the pathogenesis has not been fully clarified. There is evidence that mesangial C3 deposition plays a role in the development of the disease. The aim of this study was to examine the effect of C3 deposition on the prognosis of IgAN patients.

Method

The study included 1135 patients with IgAN confirmed by biopsy using the datatbase of the Turkish Nephrology Association Glomerular Diseases Working Group (TSN-GOLD). Patients were excluded from the study if they were aged <18 or >75 years, or if C3 staining had not been performed in the immunofluorescent analysis. C3 deposition was defined as immunofluorescent staining within the mesangium as 1+ negative and no staining, and 2+ and 3+ positive intensity staining (<2+ and ≥2+). Evaluation was also made according to the Oxford MEST-C classification. The primary endpoint was the development of end-stage renal failure (ESRF), and kidney transplantation, and an increase of 30% in glomerular filtration rate (GFR) compared to the basal value, or an elevation in proteinuria to a nephrotic level (3.5 gr/day) were accepted as poor prognosis.

Results

Mesangial C3 deposition was determined in 603 (53.1%) patients. In the evaluation of basal values between the groups with and without deposition, no statistically significant difference was determined in respect of age, gender, BMI, proteinuria level, or the presence of hypertension. In the follow-up period of mean 78 months survival, no significant difference was determined between the two groups in respect of the primary endpoint (C3+:53.1% vs. C3-:46.9%, p = 0.43). A significant correlation was determined between C3 deposition and segmental glomerulosclerosis (S1) according to the Oxford MEST-C classification (p = 0.001).

Conclusion

Although a correlation was seen between mesangial C3 deposition and the S1 MEST-C classification, the use of these alone or together as a prognostic factor in IgAN is not appropriate.
#5596 MODERATE AND SEVERE KIDNEY DYSFUNCTION ASSOCIATED WITH LEFT VENTRICLE DIASTOLIC DYSFUNCTION: A COHORT WITH DATA FROM ELECTRONIC HEALTHCARE RECORDS
Authors: Porras Cindy P , Bots Michiel , Verhaar Marianne , Vernooij Robin
Published: June 2023

Background and Aims

Left ventricular diastolic dysfunction is observed in patients with chronic kidney disease (CKD) and may lead to heart failure with preserved ejection fraction (HFpEF). In this study, we investigate the association between kidney dysfunction and left ventricular diastolic dysfunction (LVDD) in a cohort using data from electronic healthcare records.

Method

We utilized electronic healthcare data from the Utrecht Patient Oriented Database (UPOD), including all patients treated at University Medical Center Utrecht (UMCU), a university teaching hospital. We extracted demographic patient data, admission data, medication orders, and laboratory results. All performed echocardiography from baseline (i.e., first visit to the hospital) to end of follow-up (i.e., death or censoring) were included. The estimated glomerular filtration rate (eGFR) was calculated using the creatinine formula without ethnicity. Participants were divided into four groups depending on their eGFR (mL/min/1.73 m2) as follows: normal kidney function (eGFR ≥ 90), mild kidney dysfunction (eGFR ≥ 60–89), moderate kidney dysfunction (eGFR ≥ 30–59), and severe kidney dysfunction (eGFR < 30). The association of eGFR with E/A and E/e’ ratio was tested by multivariable adjusted cox proportional hazards survival analysis, reporting hazard ratios (HR) and 95% confidence intervals (CI).

Results

We identified 6,216 participants who received echocardiography as part of their routine care between 2012 and 2022. The mean age was 66.9 (SD: 12.04 years), and 41.7% of individuals were females. In total, 90.4% and 24.5% of the patients had, respectively, hypertension and diabetes. Twenty-six per cent of participants had normal kidney function, 48.2% had mild kidney dysfunction, and 21.3% and 4% had moderate and severe kidney dysfunction, respectively.  In total, 16,935 echocardiography were performed. The median time from the first to the final echocardiography was 0.78 (IQR: 2.89 years). Adjusted multivariable analysis showed that patients with moderate (HR: 1.19; 95% CI: 1.09, 1.31) and severe kidney dysfunction (HR: 1.36; 95% CI: 1.14, 1.62) had higher probabilities of having E/A ratio <0.75 or >1.8 compared with those with normal kidney function. Similarly, for an E/e’ ratio >14, participants with moderate and severe kidney dysfunction had higher probabilities, HR: 1.62 (95% CI: 1.49, 1.77) and 2.10 (95% CI: 1.83, 2.42), respectively, compared with participants with normal kidney function.

Conclusion

Moderate and severe kidney dysfunction are independently associated with LVDD. This association is independent of sex, age, hypertension, and diabetes status and is stronger for severe kidney dysfunction. Early recognition of LVDD in kidney dysfunction might help identify those at highest risk of developing HFpEF.
#5854 RENAL TRANSPLANTATION: THE BEST THERAPEUTIC OPTION FOR HEART TRANSPLANT RECIPIENTS WITH ADVANCED CKD
Authors: Redondo Gerson Berná , Cordoba Cristian , De Arizon Leonor Fayos , Mónica Pérez , Molas Carme Facundo , Guirado Lluis , Cabanas Nuria Serra
Published: June 2023

Background and Aims

Chronic kidney disease is a frequent complication of heart transplant recipients (HT) and is associated with worse survival. Current literature shows that probably the best renal replacement therapy option for these patients is kidney transplantation (KT). The aim of our work is to assess the results of renal transplantation in HT recipients.

Method

Retrospective descriptive single-center study including all heart transplant recipients patients who received a kidney transplantation in our center between 1992 and 2022. Data on renal and overall vital survival as a well as the factors that could have influenced them and associated complications were analyzed.

Results

We included 14 patients, 64% men, with a mean age of 56 years at the time of the KT. A total of 30.8% received an anticipated KT. A total of 85.7% received a KT from a cadaveric donor. In 90% the induction immunosuppression consisted of thymoglobulin, prednisone, mycophenolate, and differed tacrolimus. The mean time between heart and kidney transplantation was 15 years. Six months after KT the mean GFR was 40 mil/min/1,73 m2, at 12 months 35 ml/min/1,73 m2 and at 5 years 30 ml/min/1,73 m2. Renal graft survival was 84% and patient survival was 93% at 10 years. Regarding complications, the most frequent were urological (38.5%) followed by infectious (30.8%). The incidence of acute rejection was 18%.

Conclusion

Our data confirms that kidney transplantation in heart transplant recipients has very positive results. It is necessary to promote collaboration between CT and RT units with the aim of identifying promptly those patients who are candidates for KT, being able to perform it in the best conditions (preemptive transplantation, possibility of living donor transplanation).
#5990 COMPLEMENT GENES PROFILE OF PATIENTS WITH SEVERE HYPERTENSION AND RENAL THROMBOTIC MICROANGIOPATHY
Authors: Akaeva Mariam , Bobrova Larisa , Kozlovskaya Natalia , Vorobyeva Olga , Stolyarevich Ekaterina , Shatalov Peter
Published: June 2023

Background and Aims

Hereditary or acquired complement system dysregulation found to be driving cause of endothelial damage in atypical haemolytic uremic syndrome (aHUS) – ultrarare life-threatening disease, that always manifests with renal thrombotic microangiopathy (TMA), resulting in poor outcome in absence of appropriate treatment. Nevertheless, several studies show high incidence of rare genetic variants of complement system in other TMA’s, including hypertension-induced TMA. Here we report results of complement genes screening in patients (pts) with histologically identified renal TMA and severe hypertension in Russia, at first diagnosed as hypertension-induced TMA.

Method

A total of 28 Caucasian pts diagnosed with renal TMA (confirmed by kidney biopsy in all cases) and severe hypertension enrolled in the study. The main characteristic of the clinical picture was the absence of microangiopathic hemolysis and thrombocytopenia in prevailing of the pts, thus most of the primary and secondary causes of TMA clinically excluded. Examination of DNA samples was performed in all pts using next generation sequencing (NGS) technology. For statistical analysis continuous variables were presented as Mean (±Standart deviation) or Median (interquartile range) as appropriate.

Results

Baseline demographic and clinical characteristics of group are listed in Table 1. 13 pts (46%) had malignant form of hypertension (MHT) confirmed by eye examination. Mean systolic arterial pressure (SAP) observed at the time of presentation was 210±29 mmHg, mean diastolic arterial pressure (DAP) was 122±19 mmHg. Kidney morphology revealed chronic TMA lesions in 12 pts (43%), acute and chronic alterations simultaneously detected in 13 pts (46%). Predominantly acute lesions with glomerular and extraglomerular thrombi found in 3 (11%) pts only. Complement genes abnormalities revealed in 7 (25%) out of 28 pts. Complement factor I (CFI) rare variants were found in 2 pts (CFI c. 772A), one of this pts also had additional variant in complement factor H related protein 4 (CFHR4 c.766G>A). Complement factor C3 rare variant was observed in 1 pt (C3 c.2203C>T), membrane cofactor protein (MCP or CD46) rare variant in 1 pt (CD46 c. 198A>T), complement factor H related protein 5 (CFHR5) variant detected in 1 pt (CFHR5 c.136C>T), homozygous deletion of CFHR1 and CFHR3 detected in 1 pt and heterozygous deletion of the same complement factor H related protein genes found in another pt.

Conclusion

A quarter of pts with TMA and severe hypertension may have genetic defects in the complement system. These results confirmed that complement-mediated HUS may be misdiagnosed as hypertension-induced TMA. Lack of convincing hematological signs of TMA is common in this group, making aHUS diagnosis more sophisticated.
#6395 TUBULORETICULAR INCLUSIONS: A NEW PROGNOSTIC BIOMARKER IN KIDNEY TRANSPLANTATION
Authors: Gleeson Sarah , Beadle Jack , Moran Linda , Fitzgerald Ted , Roufosse Candice , Willicombe Michelle
Published: June 2023

Background and Aims

Tubuloreticular inclusions (TRIs) seen on electron microscopy (EM) are classically associated with lupus nephritis (LN) and systemic viral infections in native biopsies. Traditionally a marker for enhanced type I interferon expression, little is known about their significance post-transplant. We aimed to look at a large cohort of transplant biopsies showing TRIs to investigate associations and outcomes.

Method

A retrospective analysis was performed on two prospective databases; an in-centre transplant registry and a histopathology database holding data on all kidney biopsies performed at our centre. All patients biopsied since 2015, who had EM examination were included. Where patients had more than one biopsy showing a TRI the earliest one was included. Demographic, clinical and transplant data was collected from the laboratory records.

Results

2283 kidney transplant biopsies were performed between January 2015 and November 2022; 1898 (83.1%) had EM performed. Of 1898 with EM, 176 (10.8%) had evidence of TRIs. Of 176 patients, 34% were female, the median age was 52.2 (38.9-59.4) years, 32% had underlying glomerulonephritis as their cause of ESKD, 65% were deceased donors and 75% were of non-white ethnicity. TRIs were associated with serological evidence of autoimmunity (16%), viral infections (26%) and donor specific antibodies (28%), with no association found in 41%. Rejection occurred in 49%, including 31% of patients with no recognised association with TRIs. Allograft outcomes were poor, with all-cause allograft survival and death-censored allograft survival of 66% and 60%, after a follow up of 1.9 +/− 1.8 years post index biopsy. A comparison with a matched control group is planned

Conclusion

In extension to previous work, we show that TRIs appear to be associated with alloimmunity. In this regard they may be a useful biomarker especially in cases where the diagnosis is unclear or biopsy findings are ‘subthreshold’. Irrespective of aetiology, TRIs are associated with poor outcomes and warrant further consideration.
#2550 THE ANTI-AGING FACTOR, α-KLOTHO EXPRESSION DURING HUMAN PREGNANCY AND ITS COMPLICATIONS: PREECLAMPSIA AND SMALL-FOR-GESTATIONAL-AGE NEONATE
Authors: Nakhoul Farid , Shehada Sabren , Tadmor Hagar , Khateeb Nardeen , Farber Evgeny , Perlitz Yuri
Published: June 2023

Background and Aims

Pre-eclampsia (PE) is defined as arterial hypertension associated with proteinuria and may cause dysfunction of vital organs as kidney, liver, brain and other organs. PE is consider as the leading cause of maternal and perinatal morbidity worldwide [1,2]. IUGR definition is abnormal fetal growth compared with growth potential of a specific infant. α-Klotho (αKL) protein has three isoforms: a single transmembrane (mKL) form, a shed soluble form, and a secreted soluble circulating protein (sKL). mKL is expressed in the kidney and placenta. Nowadays, αKL levels correlation to pregnancy or pregnancy's complications, such as preeclampsia (PE) or intra-uterine growth restriction (IUGR) is not clear. The research goals were to monitor αKL concentrations during pregnancy and to investigate its expression alterations in correlation to pregnancy complication [3,4,5].

Method

The research included 49 participants, recruited at the Baruch Padeh Poriya medical center, Obstetric Department. The participants were divided into two groups: healthy and complicated pregnancy (PE, IUGR or both). Blood and urine samples were collected during pregnancy and post-delivery (PD). Placental samples were subjected to biochemical (WB) and Elisa), morphological (H&E) histological (IHC) staining and genetic analysis (qPCR). αKL activity was assessed using specific assigned Elisa kit.

Results

sKL during pregnancy show constant concentration that was similar in both healthy and complicated pregnancy. Significant decrease was measured in PE in sKL concentration at PD compared to its level during pregnancy. αKL activity was dramatically reduced in complicated pregnancies compared with healthy pregnancy during and PD. Placental tissue section staining presents decrease in mKL level in the placenta of complicated pregnancy group compared with healthy group. Additionally, we found significant decline in the expression of mRNA of mKL in PE/IUGR placentas compared with healthy group.

Conclusion

1. sKL level was similar in both healthy and complicated pregnancy, our results suggest low activity of sKL in complicated pregnancy compared with control. 2. Complicated pregnancy is manifested in decline in mKL, also with low activity of sKL compared with control, and gene expression between healthy and complicated pregnancy. 3. A dramatic and significant decline in NO molecules concentration in urine of complicated pregnancy compared with healthy pregnancy.
#2771 PRESCRIBING PATTERNS IN GREEK HEMODIALYSIS PATIENTS: A MULTICENTER PHARMACOEPIDEMIOLOGY STUDY
Authors: Neofytou Ioannis , Kantartzi Konstantia , Roumeliotis Stefanos , Manolopoulos Vangelis , Thodis Elias , Panagoutsos Stylianos
Published: June 2023

Background and Aims

The aim of the study is to investigate the prescribing patterns and polypharmacy in Greek hemodialysis patients and make comparisons between renal units. Polypharmacy and hyperpolypharmacy emerged as a concerning problem, that affects patient's adherence, causes drug-drug interactions, adverse drug events, increases morbidity and economically strains the health system. Patients in Europe, are prescribed on average 10–12 drugs despite recommendations on polypharmacy.

Method

This is a multicenter retrospective study (2018-2021), in Northeastern Greece, of 270 patients (male = 168, female = 102) with mean age of 63.8±15 years and median dialysis duration of 45(18-96) months. The medications and laboratory values were documented for a period of 12 months, provided that there were no major changes on their therapy that time. The 4 public health dialysis units participating on the survey, were classified as secondary (179 patients) and tertiary care (91 patients) depending on the bed capacity (>600) and the availability of health services. Statistical analysis was conducted using SPSS ver26.

Results

The mean number of prescribed medications was 10.4 (SD 2.9, range 2–20). Of the participants, 97.4% were experiencing polypharmacy (≥5 medications per person) and 62.6% hyperpolypharmacy (≥10 medications). The average number of prescribed medications in tertiary care was substantially lower comparing with secondary care (mean: 8,7 vs 11,3, p<0.001). The difference in the mean number, remained significant even when the result was adjusted for age, gender, cardiovascular disease, primary disease and dialysis duration. Notably, despite the fewer medications, there was no statistically significant difference between the two groups, in achieving the most recent Kidney Disease Improving Global Outcomes (KDIGO) guidelines for URR (Urea Ruction Ratio), renal mineral bone disease and renal anemia (chi-sqaure, p>0.05 for all variables). The most frequently prescribed group of medications were EPO analogues (87%), Vitamin D supplements (83%), Proton Pump Inhibitors (68%), β-blockers (56%), Antiplatelets (45%) and Loop diuretics (37%). It is important to note the alarming number of patients receiving medication for mental illness (35.2%), mainly benzodiazepines (26%), with women to be more vulnerable (42.2% vs 30.1%, OR:1.63).

Conclusion

This study reports that Greek prescribing practices follow the same worrisome patterns as other European countries. Rural hospitals appear to prescribe more drugs than tertiary facilities.
#2789 HIGHER MORTALITY RISK WITH CHRONIC KIDNEY DISEASE IN TYPE 2 DIABETES IN YOUNGER AGES: A DANISH NATIONWIDE COHORT STUDY 2014-2018
Authors: Nyeland Martin , Rørth Rasmus , Carstensen Bendix , Persson Frederik , Rossing Peter , Vistisen Dorte
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is a frequent complication to diabetes. CKD is associated with significantly increased risk of morbidity and mortality among people with diabetes. It is well known that the incidence and progression of CKD differ between men and women. Women are more likely to get CKD, while men have a more rapid progression of the disease. However, previous studies were based on small populations. We aimed to investigate the mortality with and without CKD in men and women with type 2 diabetes (T2D).

Method

Secular and age trends in mortality rates and sex differences were investigated in a dynamic, nationwide cohort of people with T2D. CKD was defined based on hospital diagnosis, procedure codes and laboratory measurements. Mortality rates were modelled as an age-period-cohort model using Poisson models with log person time, smooth effects of current age, and calendar time (date of follow-up), separate for each sex and CKD status.

Results

The study included 304,956 persons (55,9% men) and 1,2 million person-years. 87,696 persons were recorded with CKD, of which 34,967 persons had a CKD event during follow-up. The overall mortality rate was 37.8 [37.4; 38.2] versus 31.1 [30.4; 31.7] per 1000 person-years for people with T2D, without and with CKD, respectively. The mortality rate for people with T2D and CKD is larger and more pronounced in the younger ages. For elderly people the mortality rate is larger for people with T2D and without CKD. In general, mortality for men is higher than mortality for women at all ages, observed for both people with and without CKD. The overall secular trend per year was increasing for persons without CKD 2.0 [1.8; 2.2] %/year. For those with CKD, a decrease −2.4 [−2.1; −2.6] %/year was observed, decreasing until start 2017 followed by an increase. The overall M/F mortality ratios were 1.23 [1.20; 1.25] and 1.91 [1.83; 2.00], respectively.

Conclusion

The observed larger and more pronounced mortality rate for people with T2D and CKD in the younger ages, suggests a potential for early preventive intervention among young adults. Supported by an unrestricted grant from Bayer.
#2880 ASSESSMENT OF FLUID STATUS BY COMBINATION OF LUNG ULTRASOUND, BIOIMPEDANCE, AND INFERIOR VENA CAVA MEASUREMENT IN HEMODIALYSIS PATIENTS
Authors: Ekart Robert , Martin Oriol Portals , Soto Ricardo López , Galuf Tina Stropnik , Hojs Radovan
Published: June 2023

Background and Aims

Assessment of fluid status in hemodialysis patients (HD) remains a major challenge for nephrologists. Fluid overload is one of the most common modifiable risk factors directly associated with hypertension. The purpose of our study was to investigate whether the combination of three bedside methods-lung ultrasound comets (LUC), multifrequency bioimpedance (MBIS), and inferior vena cava diameter (IVCD) measurement-could provide complementary information to guide the management of HD patients.

Method

We assessed MBIS, LUC at 28 typical sites, and IVCD in 18 HD patients enrolled in the HD maintenance program. LUC and IVCD measurements were performed three times-before, during, and after HD, MBIS only before and after HD. For MBIS measurement, we used the Body Composition Monitor (Fresenius Medical Care, Bad Homburg, Germany), and for LUC and IVCD, we used an ultrasound machine (Esaote MyLabOmega, Genoa, Italy). Ultrafiltration during HD was not adjusted for LUC, IVCD, and MBIS. Overhydration (OH) was defined as > 2L with MBIS, > 15 LUC, and < 40% collapsibility index (CI) on IVCD.

Results

The mean age of participants was 61 (IQR, 47-74) years, and thirteen (72.2%) were male. The average dialysis vintage of our patients was 105 months (IQR, 30-155). According to the OH criteria before, during, and after HD, 13 (72%), 2 (11%) patients were overhydrated according to MBIS, 10 (56%), 7 (39%), 3 (17%) patients according to LUC, and 13 (72%), 12 (67%), and 11 (61%) patients according to CI. We found no correlation between systolic blood pressure (BP), diastolic BP, MBIS, LUC, and CI before, during, and after HD, except that systolic BP after HD correlated with MBIS (OH) after HD (r = 0.491; p = 0.039). Using the paired-samples T-test, we found a statistically significant difference between OH before and after HD (p < 0.001), between LUC before and during HD (p = 0.006), between LUC during and after HD (p = 0.002), and between LUC before and after HD (p < 0.001). Using the paired-samples T-test, no statistically significant difference was found between systolic, diastolic BP and CI before, during, and after HD.

Conclusion

Optimal assessment of fluid status in HD patients remains challenging and, according to our results, may require a combination of LUC and MBIS parameters.
#2935 PHARMACOLOGICAL BLOCKADE OF NMDA RECEPTOR DECREASES KIDNEY INJURY INDUCED BY LIPOTOXICITY IN VITRO AND IN VIVO
Authors: Sanjuan Auria Eritja , Enriquez Maite Caus , Bardaji Ana Martinez , García-Carrasco Alicia , Diaz-Tocados Juan Miguel , Revilla José Manuel Valdivielso , Giráldez Elvira Fernández , Bozic Milica
Published: June 2023

Background and Aims

Obesity and hyperlipidemia are well established risks factors for kidney injury that can lead to chronic kidney disease (CKD). N-methyl-D-aspartate receptors (NMDARs) are expressed in the kidney and they are involved in the pathology of different renal diseases. The main objective of this study was to establish the role of the NMDAR in the lipotoxicity-induced kidney injury.

Method

In vivo, we used C57BL/6J mice fed a normal diet (ND) and high fat diet (HFD), as well as mice co-treated with HFD and NMDAR antagonists (HFD+memantine and HFD+MK-801). In vitro, we used renal proximal tubular epithelial cells (HK-2) treated with free fatty acids (FFAs) and a combination of FFAs and NMDAR antagonists. Lipid accumulation was analysed using Oil-Red staining. Expression of NMDAR1 and inflammation, fibrosis and oxidative stress markers were assessed by qPCR and western blot.

Results

After 10 weeks of diet, mice fed a HFD showed elevated levels of lipids in serum and kidney, compared with the ND. HFD induced an increase of expression of renal NMDAR mRNA and protein, as well as the expression of IL6, ICAM1, MCP1, TNFα and IL1β mRNA. Furthermore, HFD induced an increase of αSMA, vimentin, TGFβ1, fibronectin, OPN and NGAL levels in the kidney. Co-treatment with NMDAR antagonists significantly decreased levels of inflammatory markers, as well as the renal expression of αSMA, OPN and NGAL, but it did not have any effect on the hyperlipidemia induced by HFD. In vitro, treatment of HK-2 with different concentrations of FFAs induced accumulation of lipids in the cell, as well as the increase of the expression of NMDAR1 and markers of inflammation and oxidative stress. Co-treatment with NMDAR antagonists reversed changes induced by FFAs in HK-2 cells. The results were confirmed at the protein level.

Conclusion

Our results indicate that the NMDAR could be a new therapeutic target in the lipotoxicity-induced kidney injury.
#2997 ASSESSMENT OF FRACTURE RISK IN KIDNEY TRANSPLANT RECIPIENTS BY FRAX SCORE WITHOUT BONE MINERAL DENSITY
Authors: Elsharkawy Magdy , Emara Ahmed , Elbraky Abdelrahman , Abdelmegied Shaimaa Zaki
Published: June 2023

Background and Aims

Bone disease post-transplantation is a major cause of morbidity in kidney transplant (KT) recipients, with a significantly higher risk of fractures and mortality. This study investigated the added value of calculated 10-year fracture risk for major osteoporotic fracture (MOF) and hip fracture by frax score with an assessment of risk factors in KT recipients.

Methods

A cross-sectional study included 71 live-related KT recipients. Demographic, clinical, and laboratory data were recorded. The 10-year fracture risk for MOF and hip fracture were calculated using frax score without bone mineral density in recipients who completed at least 1 year after KT.

Results

The prevalence of MOF (>3% risk of fracture) was 14.1%(10 patients), MOF (<3% risk of fracture) was 85.9% (61 patients). A high hip fracture score (>3% risk of hip fracture) was in 10% (1 patient). There was a significant difference between both groups (>3%vs <3% fracture risk) in age, MOF score, hip fracture score, and serum albumin p-value were <0.00001, <0.00001, 0.000134, and 043009 respectively. The analysis of demographic data of the patients with a score (>3% fracture risk) showed that 70% were males (7 patients), 50% (5 patients) had BMI>30 and the main cause of ESRD pre-transplant was lupus nephritis and glomerulonephritis in 50% (5 patients) that exposed for long periods of immune suppression pre-transplant. In 80% (8 patients) were 1st transplant, 10% (1 patient) were 2nd transplant, and 10% (1 patient) was a combined liver-kidney transplant. The rejection episode was zero%. There was a significant difference in patients' fracture risk >3% in phosphorus pre-transplant versus post-transplant p-value 0.01.

Conclusion

Frax score without bone mineral density has shown a low percent of fracture risk (<3%) in most kidney transplant recipients and high scores were associated with high BMI, phosphorus, and exposure pre-transplant to immune suppression.
#3015 EFFECT OF DAPAGLIFLOZIN ON ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES AND CKD
Authors: Abdullaev Sherzod , Sharapov Olimkhon
Published: June 2023

Background and Aims

Albuminuria in patients with diabetes presents a higher risk for adverse renal and cardiovascular (CV) outcomes. Sodium-glucose co-transporter 2 (SGLT2) inhibitors demonstrate improved albuminuria and reduces the risk of end-stage renal disease in patients with chronic kidney disease. The study aim was the impact of the SGLT2 inhibitor dapagliflozin on urine albumin-to-creatinine ratio (UACR) and GFR decline.

Method

In the single center trial, total 132 participants with CKD and type 2 diabetes (T2D) were randomly assigned to dapagliflozin (n = 78) 10 mg once daily or placebo (n = 54). Kidney inclusion criteria were eGFR 30-60ml/min/1.73 m2 and any UACR. The primary end point was a composite of sustained decline in eGFR ≥50%, end-stage renal disease, or kidney or cardiovascular death. Percentage treatment difference was estimated by geometric mean ratio for the overall cohort and by eGFR and UACR subgroups. Progression/regression of UACR were assessed. Hazard ratios, 95% confidence intervals (CI), and p-values were estimated by Cox proportional hazards model.

Results

Median baseline eGFR was 42.3ml/min/1.73 m2, with 5% at <30ml/min/1.73 m2. At baseline, median UACR was 103 mg/g, and 1/4 of patients had normoalbuminuria, 2/4 had micro, and 1/4 had macroalbuminuria. Median follow up was 18 months. The UACR difference for dapagliflozin vs placebo was -25.1% (95% CI -27.5, -23.2; p<0.001). Reductions were similar across eGFRs. In UACR 30-299mg/g and ≥300mg/g, reductions were significant in dapagliflozin (p<0.001). Progression risk was lower and regression risk higher in dapagliflozin vs placebo (p<0.001).

Conclusion

Dapagliflozin significantly slowed long-term eGFR decline in patients with CKD with T2D compared with placebo, and significantly reduced UACR and had favorable effects on UACR progression and regression.
#3075 EFFECT OF KIDNEY TRANSPLANTATION ON CARDIORESPIRATORY FITNESS ASSESSED WITH CARDIOPULMONARY EXERCISE TESTING: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Pella Eva , Alexandrou Maria Eleni , Boutou Afroditi , Theodorakopoulou Marieta , Sampani Erasmia , Dipla Konstantina , Zafeiridis Andreas , Sarafidis Pantelis
Published: June 2023

Background and Aims

Patients with kidney failure often present with reduced functional cardiovascular reserve and exercise intolerance. Kidney transplantation is the optimal treatment for patients with end-stage kidney disease as it is associated with longer survival and improved quality of life compared to hemodialysis or peritoneal dialysis.

Method

This is a systematic review and meta-analysis of studies using cardiopulmonary-exercise-testing (CPET) to examine the cardiorespiratory fitness of patients with kidney failure before and after kidney transplantation. The primary outcome was differences in pre- and post-transplantation values of peak oxygen uptake (VO2peak). Literature search involved PubMed, Web of Science and Scopus databases, manual search of article references and grey literature. Quality assessment was undertaken with Newcastle-Ottawa-Scale.

Results

From 379 literature records initially retrieved, 6 studies (207 participants) were included in final meta-analysis. A marginal, but not significant, improvement was observed in oxygen consumption during peak exercise compared to pre-transplantation values (standardized mean difference [SMD]: 0.32, 95%CI −0.02; 0.67). Oxygen consumption at anaerobic threshold (VO2AT) was significantly improved after kidney transplantation (weighted MD [WMD]: 2.30 ml/kg/min, 95%CI 0.50; 4.09), whereas no significant changes were observed in maximum heart rate (WMD: 10.45 bpm, 95%CI −3.97; 24.86). In subgroup analysis, consistent results were shown between patients having undergone transplantation preemptively and those after dialysis initiation (p-value for subgroup differences = 0.95). Of note, a trend for improvement in VO2peak was observed when pooling data reported from follow-up assessments undertaken at least 3 months post-transplantation surgery (SMD: 0.17, 95%CI −0.03; 0.38), but not earlier (WMD: −0.03 ml/kg/min, 95%CI −4.28; 4.23).

Conclusion

Several major indices of cardiorespiratory fitness tend to improve after kidney transplantation compared to pre-transplantation values. This finding may represent another modifiable factor contributing to better survival rates of kidney transplant recipients compared to patients undergoing dialysis.
#3093 PROGNOSTIC FACTORS AND VALIDATION OF THE HISTOLOGIC CHRONICITY SCORE FOR C3 GLOMERULOPATHY: A REGISTRY ANALYSIS
Authors: Mirioglu Safak , Cebeci Egemen , Yazici Halil , Derici Ulver , Sahin Gulizar Manga , Eren Necmi , Gungor Ozkan , Dede Fatih , Dincer Mevlut Tamer , Turkmen Kultigin , Basturk Taner , Duranay Murat , Arikan Izzet Hakki , Tunca Onur , Elçioğlu Ömer Celal , Tatar Erhan , Aydin Zeki , Oygar Deren , Demir Serap , Tanrisev Mehmet , Kurultak Ilhan , Oruc Aysegul , Turkmen Aydin , Akcay Omer Faruk , Çetinkaya Hakkı , Ozturk Savas
Published: June 2023

Background and Aims

Data on prognostic factors of C3 glomerulopathy (C3G) are limited, and validation of the new C3G histologic index (C3G-HI) in different settings is still needed. We aimed to evaluate the chronicity score of C3G-HI and probable prognostic factors in our population.

Methods

In this prospective registry, 99 patients with C3G were identified, and 74 patients from 20 centers with adequate follow-up data were included. Total chronicity score (TCS) (0-10) was calculated according to percentages of glomerulosclerosis, interstitial fibrosis (IF), tubular atrophy (TA), and presence of arterio- and arteriolosclerosis [1]. Study outcome was defined as doubling of serum creatinine from baseline, undergoing dialysis or transplantation, development of stage 5 chronic kidney disease (eGFR <15 ml/min/1.73 m2 by CKD-EPI 2009 equation), or death.

Results

Baseline features, treatment characteristics and outcomes were detailed in Table 1. Median follow-up duration was 36 (12-60) months. Overall, 19 patients (25.7%) experienced the study outcome over a median of 24 (6-51) months. Three patients died due to infections (n = 2) and unknown causes (n = 1) including a patient who died shortly after becoming dialysis-dependent. Median TCS was 3 (1-5). Univariate analyses showed that IF, hemoglobin, serum creatinine and serum albumin levels were associated with the outcome, but only grade 3 IF predicted the outcome in multivariate Cox regression (HR: 6.623, 95% CI: 1.269-34.564, p = 0.025). Since the median follow-up was 36 months, separate analyses for the outcome at 3 years were conducted. IF, TA, TCS, hemoglobin, serum creatinine and albumin were associated with the outcome in univariate analyses. In a multivariate Cox regression model encompassing IF, TA, hemoglobin, serum creatinine and albumin, only hemoglobin was identified as a predictor. A second model including TCS instead of IF and TA demonstrated that TCS (HR: 1.288, 1.021-1.626, p = 0.033) and hemoglobin (HR: 0.617, 0.407-0.935, p = 0.023) predicted the study outcome. Kaplan-Meier analysis showed that 3-year kidney survival was lower in patients with TCS ≥4 (72.4%) compared to TCS <4 (91.1%) (p = 0.036) (Figure 1).

Conclusions

TCS ≥4 and lower hemoglobin levels at diagnosis predict the 3-year kidney survival in patients with C3G, which validates the chronicity score of C3G-HI.