Glomerular Filtration Research Articles

Effect of Parathyroidectomy After Renal Transplantation on Grafted Kidney Function Within One Year: A Meta-Analysis

Objective: Secondary hyperparathyroidism (sHPT) is a common symptom of chronic kidney disease (CKD), and at the time of transplantation, more than two-thirds of patients with end-stage renal disease have secondary hyperparathyroidism. After kidney transplantation, parathyroid function is normalized in some kidney transplant recipients, but up to 50% of kidney transplant recipients develop tertiary hyperparathyroidism (tHPT) one year after kidney transplantation. The effect of parathyroidectomy on the grafts is currently unclear, so we conducted a meta-analysis of these studies to assess the changes in graft function one year after parathyroidectomy after kidney transplantation to investigate the resection in renal transplant recipients. Methods: A thorough exploration was conducted across Embase, PubMed, Web of Science, and the Cochrane Library databases to gather pertinent literature spanning from January 1, 2000, to December 31, 2023. The search criteria encompassed terms such as "kidney transplantation," "parathyroidectomy," and "hyperparathyroidism." Results: Twelve studies were scrutinized to assess alterations in graft functionality at 1, 3, 6, and 12 months post-parathyroidectomy. The meta-analysis unveiled a notable decline in overall glomerular filtration rate and a concurrent elevation in serum creatinine one year post-parathyroidectomy, signifying an impairment in graft function compared to the preoperative phase. Significant heterogeneity was observed among the studies. Conclusion: Following parathyroidectomy in renal transplant recipients one year post-surgery, calcium and parathyroid hormone levels normalized. Nonetheless, there was evident impairment in graft function and an elevated risk of graft loss. Hence, the safety of parathyroidectomy in patients with secondary hyperparathyroidism post-renal transplantation necessitates meticulous consideration.

Prolonged ischaemia during partial nephrectomy: impact of warm vs cold.

To evaluate the impact of prolonged ischaemia during partial nephrectomy (PN), which remains understudied despite its potential clinical relevance. Of 1371 patients managed with on-clamp PN (2011-2014), 759 (55%) had imaging and assessment of serum creatinine levels before and after PN within the appropriate timeframes necessary for inclusion. This timeframe was chosen to allow for a robust analysis of both warm and cold ischaemia. Recovery from ischaemia (Recischaemia) was defined as ipsilateral glomerular filtration rate (GFR) preserved, normalized by percentage ofparenchymal volume preserved (PPVP), and would be 100% if all nephrons recovered completely from ischaemia. Pearson correlation and multivariable linear regression models were used to assess associations between Recischaemia and ischaemia type and duration. Of 759 patients, 525 (69%) were managed with warm ischaemia. The median warm/cold ischaemia times were 22 and 30 min, respectively. Overall, the median percent ipsilateral GFR preserved, PPVP and Recischaemia were 79%, 83% and 96%, respectively. Segmented regression analysis demonstrated substantially greater decline in Recischaemia, beginning at approximately 30 min for warm ischaemia, which was not observed for hypothermia. Prolonged ischaemia (defined as >30 min) occurred in 197 patients (26%; 88 warm/109 cold). For limited ischaemia (≤30 min), hypothermia was often used for tumours with increased tumour size and complexity (P < 0.01), while for prolonged ischaemia, the warm/cold subgroups had similar patient and tumour characteristics. For limited ischaemia and prolonged hypothermia, median Recischaemia remained >95%, independent of ischaemia time. Differences in Recischaemia between the warm and cold cohorts became significant only after 30 min (P < 0.05). On multivariable analysis, prolonged warm ischaemia was associated with reduced Recischaemia (P = 0.02), which fell 3.9% for every additional 10 min beyond 30 min. Our data suggest that Recischaemia begins to decline significantly after 30 min during PN, although hypothermia was protective. Avoidance of prolonged warm ischaemia should be prioritized in patients with solitary kidneys and/or significant pre-existing chronic kidney disease.

IDiabetes platform—enhanced phenotyping of patients with diabetes for precision diagnosis, prognosis and treatment: study protocol for a cluster-randomised controlled study in Tayside, Scotland

Introduction and aimDiabetes is a global health emergency with increasing prevalence and diabetes-associated morbidity and mortality. One of the challenges in optimising diabetes care is translating research advances in this...

Interferon-α as a biomarker to predict renal outcomes in lupus nephritis

ObjectiveTo determine if serum interferon (IFN)-α levels at the time of a lupus nephritis (LN) flare are associated with renal outcomes.MethodsPatients with an LN flare who had a preflare estimated...

Co-occurrence of Charcot-Marie-Tooth disease type 1 and glomerulosclerosis in a patient with a de novo INF2 variant

BackgroundRenal disease is associated with Charcot-Marie-Tooth disease (CMT), a common inherited neurological disorder. Three forms of CMT have been identified: CMT1 of the demyelinating type, CMT2 of the axonal defect type, and intermediate type (Int-CMT). INF2 is an important target for variants that cause the complex symptoms of focal segmental glomerulosclerosis (FSGS) and CMT.Case presentationWe report the case of a 13-year-old female Chinese patient (born in 2011) with a rare co-occurrence of CMT1 and glomerulosclerosis (GS) (CMT1-GS). The patient presented with slowly progressive gait disorder with unsteadiness during walking, pes cavus, and kyphoscoliosis since the age of 1 year. Electrophysiological studies and brain magnetic resonance imaging revealed demyelinating features consistent with CMT1. At 12 years of age, she was hospitalised for hypertension and dizziness; her serum albumin was 27.9 g/L, serum creatinine was 87 μmol/L, estimated glomerular filtration rate was 88.6 mL/min, and 24-h urine protein was 4.95 g. A renal biopsy showed glomerulosclerosis. Renal function deteriorated further during the follow-up period, and she received a kidney transplant at the age of 13. Whole-exome sequencing identified a de novo heterozygous c.326T > G (p.Met109Arg) variant in exon 2 of INF2. The variant was classified as “pathogenic” according to the American College of Medical Genetics and Genomics criteria.ConclusionsWe describe a rare clinical phenotype of CMT1-GS associated with a de novo variant of INF2. Our findings expand the phenotypic and genotypic spectrums of INF2-associated disorders.

The course of granulomatosis with polyangiitis (Wegener’s granulomatosis) with late ocular and orbital manifestations (clinical observation)

Granulomatosis with polyangiitis (GPA) is a granulomatous necrotizing vasculitis associated with antineutrophil cytoplasmic antibodies. The clinical picture of GPA is characterized by a wide range of manifestations, including nonspecific symptoms, signs of damage to the upper and lower respiratory tract and glomerulonephritis. The article presents the observation of a patient for 12.5 years, who at the beginning of the disease, along with complaints of malaise, weakness, decreased appetite and weight loss, had a hemorrhagic rash, proteinuria, erythrocyturia, decreased glomerular filtration rate and increased creatinine and urea levels. After a positive result for antineutrophil cytoplasmic antibodies and the results of nephrobiopsy with evidences of glomerulonephritis with the development of glomerulosclerosis and fibrosis of the crescents (pauci-immune variant) with a moderately pronounced tubulointerstitial component, the patient was diagnosed with GPA and immunosuppressive therapy was initiated. Almost 8 years after the manifestation of GPA during continuous pathogenetic therapy, the patient complained of swelling of the left eye and its increase in volume, diplopia. Computed tomography of the head revealed a mass of the left orbit. Morphological examination of the excised mass revealed its inflammatory origin as consequence of vasculitis. The special aspect of the presented case is that ocular and orbital pathologies of GPA developed in the patient 8 years after the initial manifestation of the disease against the background of ongoing immunosuppressive therapy in conditions of laboratory remission of GPA.

Right ventricular to pulmonary arterial coupling as a predictor of survival in patients undergoing mitral valve surgery for mitral regurgitation.

Right ventricular-to-pulmonary artery (RV-PA) coupling has been associated with outcomes in mitral regurgitation (MR) treated by transcatheter approaches. We evaluated RV-PA coupling as a predictor of survival and post-operative length of hospital stay (LOS) in patients with mitral regurgitation undergoing mitral valve (MV) surgery. In this retrospective analysis (median follow-up: 5.8 years), RV-PA coupling was quantified as the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) using transthoracic echocardiography (TTE). Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-point of TAPSE/PASP to predict all-cause mortality and the study population was dichotomised according to this value. The primary end-point was all-cause mortality. A secondary end-point of LOS was also assessed. Out of 142 patients (median age: 67, female: 49%), 35 showed impaired coupling at baseline (TAPSE/PASP ≤0.35). Patients with TAPSE/PASP ≤0.35 had higher absolute mortality (37% vs 8%, p < 0.001) and longer LOS (7 days vs 9 days, p = 0.04). Kaplan-Meier analysis revealed lower survival in patients with TAPSE/PASP ≤0.35 (log-rank: p < 0.0001). In multivariable Cox regression, TAPSE/PASP ≤0.35 was the most significant predictor of all-cause mortality (HR: 3.69, 95% CI: 1.31-10.1, p = 0.011), alongside chronic obstructive pulmonary disease and estimated glomerular filtration rate. TAPSE/PASP ≤0.35 was associated with significantly increased LOS (β: 4.6, 95% CI: 0.66-8.5, p = 0.022) alongside left ventricular ejection fraction, MV replacement, and urgent operation. In MR patients undergoing MV surgery, TAPSE/PASP ≤0.35 is associated with increased mortality and LOS. Further validation is indicated in larger, prospective cohorts.

Kidney hemodynamic effects of sodium-glucose cotransporter 2 inhibitors in diabetes: physiology and clinical implications

Abstract The progressive loss of kidney function in diabetes mellitus is partly attributable to the occurrence of glomerular hyperfiltration. Consequently, therapeutic interventions that lower intra-glomerular pressure are a cornerstone of treatment in diabetic kidney disease. Sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently reduce glomerular filtration rate (GFR) and calculated intraglomerular pressures across studies. However, the net effect on arteriolar tone that leads to acute GFR declines may differ between cohorts. While pre-glomerular vasoconstriction appears to be the dominant mechanism responsible for GFR dipping in patients with type 1 diabetes (T1D) and glomerular hyperfiltration, other factors, including postglomerular vasodilation, may contribute to the acute GFR decline in normofilterering individuals with T1D and type 2 diabetes. Regardless of the responsible mechanisms, acute changes in GFR are associated with long-term kidney function preservation—a relationship that may reflect an underlying protective decline in glomerular hypertension.

Outcome and Renal Safety of PSMA-Targeted Radioligand Therapy in mCRPC Patients With Preexisting Impaired Renal Function.

This study aims to evaluate the outcome and renal safety of prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) in patients with metastatic castration-resistant prostate carcinoma (mCRPC) and preexisting renal impairment. Ninety-four patients with preexisting renal impairment were included in this retrospective analysis. Inclusion criterion was a glomerular filtration rate (GFR) of ≤60 mL/min (equivalent to Common Terminology Criteria of Adverse Events [CTCAE] ≥2). Patients underwent either [177Lu]Lu-PSMA-617 RLT exclusively (n = 63) or additionally in augmented manner with [225Ac]Ac-PSMA-617 (n = 31). The median number of administered cycles was 4 (range, 1-16 cycles) with a mean cumulative activity of 29.9 ± 16.3 GBq (range, 6.9-87.2 GBq) [177Lu]Lu-PSMA-617. Main blood parameters of interest were creatinine, cystatin C, and the respective GFR values. Changes in GFR were categorized according to CTCAE v5.0. In the entire cohort, mean best PSA response was -56.73% ± 45.71%, with 63 of 94 patients (67%) experiencing partial remission. The median progression-free survival and overall survival were 6.7 and 14.1 months, respectively. Under PSMA-RLT, 5 of 94 patients (5.3%) improved to CTCAE grade 0, and 23 of 94 (24.5%) improved to CTCAE grade 1. Three of 94 patients (3.2%) improved from CTCAE grade 3 to grade 2, and only 5 of 94 (5.3%) decreased. The majority (58/94 [61.7%]) of patients stayed stable in terms of CTCAE grading. PSMA-RLT is an effective and safe treatment in mCRPC patients with preexisting impaired renal function (CTCAE ≥2). In daily clinical practice, patients should not be categorically excluded from enrolment to PSMA-RLT due to renal impairment.

Rate of decline in kidney function with age: a systematic review

ObjectiveTo determine the distribution of kidney function values as measured by glomerular filtration rate (GFR), and the rate of decline with age in male and female healthy subjects without pre-existing...

Urinary transforming growth factor beta-1 levels correlate with the effect of renorrhaphy on functional outcomes post-laparoscopic partial nephrectomy: A pilot-study

ABSTRACT Purpose Preservation of functional renal parenchyma is one of the main targets of partial nephrectomy. We investigated the effects of suture on renal parenchyma in tumor bed and on short-term renal function. Materials and Methods Patients with unilateral cT1 renal masses candidate for laparoscopic partial nephrectomy (PN) have been recruited. After tumor excision, medullary sutures were replaced by argon beam in Group 1, while Group 2 had conventional 2-layer renorrhaphy. Groups have been matched using propensity score. Transforming growth factor beta-1 (TGFb1) levels in urine have been measured at the 1st and 30th day post-PN. Glomerular filtration rate has been estimated (eGFR) at baseline and 3 months post-PN. Results Sixteen cases were matched in each group. There was no difference between groups regarding baseline, operative and perioperative data. Number of sutures in group 1 is nearly half that in group 2 (10 vs 19, respectively, p < 0.001). Group 1 showed lower urinary TGFb1 levels at the 1st and 30th day post-PN (p < 0.01 for each), higher eGFR after 3 months (p = 0.01), and less decline of eGFR from baseline (p = 0.046). Conclusion TGFb1 levels in urine after PN are related to the number of sutures. Reduced number of sutures in tumor bed has a positive effect on short term eGFR changes possibly by reducing tumor bed fibrogenic healing response as well as preserving renal parenchymal volume.

Mechanical circulatory support reduces renal sympathetic nerve activity in an ovine model of acute myocardial infarction.

The use of circulatory assist devices has been shown to improve glomerular filtration rate and reduce the incidence of acute kidney injury in patients following acute cardiac pathology. However, the mechanisms of improvement in kidney function are not clear. We tested the hypothesis that mechanical circulatory support would result in a decrease in directly recorded renal sympathetic nerve activity (RSNA) and mediate the improvement in renal blood flow (RBF) in a setting of acute myocardial infarction (AMI)-induced left ventricular systolic dysfunction. An anaesthetized ovine model was used to induce AMI (n = 8) using injections of microspheres into the left coronary artery in one group. The second group did not undergo embolization (n = 6). The effects of mechanical circulatory support using the Impella CP on directly recorded renal sympathetic nerve activity were examined in these two groups of animals. Injection of microspheres resulted in a drop in mean arterial pressure (MAP) of 21 ± 4mmHg compared to baseline values (p < 0.05; n = 8). This was associated with a 67% increase in renal sympathetic nerve activity (RSNA; from 16 ± 5 to 21 ± 5 spikes/s; p < 0.05; n = 7). Impella CP support significantly increased MAP by 13 ± 1.5mmHg at pump level 8 (p < 0.05) in the AMI group. Incremental pump support resulted in a significant decrease in RSNA (p < 0.05) in both groups. At pump level P8in the AMI group, RSNA was decreased by 21 ± 5.5% compared to pump level P0 when the pump was not on. Our data indicate that the improvement in kidney function following mechanical circulatory support may be mediated in part by renal sympathoinhibition.

Mediating role of inflammatory biomarkers on the association of physical activity, sedentary behaviour with chronic kidney disease: a cross-sectional study in NHANES 2007–2018

ObjectivesThis study aims to investigate the association of physical activity (PA) and sedentary behaviour (SB) with chronic kidney disease (CKD), and to illustrate whether inflammatory biomarkers play a mediating role.DesignA...

Association between adipose deposition and mortality among adults without major cardiovascular risk factors

AimTo examine the association between adiposity and mortality in U.S. adults without major cardiovascular risk factors. MethodsWe analyzed 7,948 adults (4,123 women, 3,825 men) aged > 20 years from the National Health and Nutrition Examination Survey (2003-2004, 2011-2016). Participants with cardiovascular disease, estimated glomerular filtration rate < 60 ml/min/1.73m², diabetes, hypertension, or pregnancy were excluded. Adiposity measures, assessed by dual-energy x-ray absorptiometry or anthropometrics, included android and gynoid fat mass index (FMI), android-to-gynoid ratio, subcutaneous, abdominal, and visceral FMI, BMI, and waist circumference. We employed multivariable-adjusted Cox regression and restricted cubic spline models to assess sex-specific associations between adiposity measures and all-cause mortality. ResultsOver a median follow-up of 7.8 years, there were 83 deaths among women and 119 among men. In women, BMI, waist circumference, and gynoid FMI showed non-linear associations with all-cause mortality, while in men, BMI, waist circumference, and android-to-gynoid ratio demonstrated similar non-linear associations. In final adjusted models, a 1-SD increase in visceral, subcutaneous, and abdominal FMI among women was associated with 61% (HR 1.61, 95% CI 1.17-2.21), 87% (HR 1.87, 95% CI 1.13-3.08), and 89% (HR 1.89, 95% CI 1.19-2.99) higher mortality risk, respectively. Women in the lowest tertile of gynoid FMI had an 82% (HR 1.82, 95% CI 1.01-3.29) higher mortality risk compared to those in the middle tertile. In final adjusted models, a 1-SD increase in gynoid, android, visceral, subcutaneous, and abdominal FMI among men was associated with 30% (HR 1.30, 95% CI 1.02-1.65), 41% (HR 1.41, 95% CI 1.09-1.83), 54% (HR 1.54, 95% CI 1.04-2.28), 69% (HR 1.69, 95% CI 1.25-2.29), and 76% (HR 1.76, 95% CI 1.25-2.48) higher mortality risk, respectively. Additionally, men in the middle tertile of android-to-gynoid ratio had a 2.68-fold higher mortality risk compared to the lowest tertile, while men in the highest BMI tertile had an 83% higher mortality risk compared to the lowest tertile. Sex modified the association between gynoid FMI and mortality (P-interaction = 0.008). ConclusionImaging-based adiposity measures have distinct prognostic value for mortality beyond traditional anthropometrics in adults without cardiovascular risk factors.

EGFR slope as predictor of mortality in heart failure patients.

Heart failure (HF) leads to an imbalance between heart and kidney function, resulting in poor outcomes. However, the prognostic significance of the estimated glomerular filtration rate (eGFR) trajectory in HF patients remains unclear. We analysed electronic health records (EHRs) of real-world HF patients, assessing eGFR trajectories and their impact on mortality. Retrospective clinical data of HF patients were processed using natural language processing. Chronic kidney disease (CKD) was evaluated, and eGFR trajectories were analysed using linear mixed-effects models. Cox proportional hazard models were used to evaluate the relationship between baseline variables and mortality, while joint modelling combined eGFR trends and mortality. The dataset comprised 1986 patients, with a mean age of 74.8years (SD±11.7) and 58% male. At the time of HF diagnosis, 58% of patients were diagnosed with CKD, and 39% presented with heart failure with preserved ejection fraction (HFpEF). The median follow-up duration was 3.16years, during which 399 patients (20%) died. Patients with CKD were significantly older and exhibited a higher prevalence of myocardial infarction (P=0.048), coronary revascularization (P=0.004), stroke (P<0.001), atrial fibrillation (P<0.001) and type 2 diabetes (P<0.001). Mortality rates at 1 and 2years were nearly twice as high in CKD patients compared with those without (P<0.001). Notably, CKD was significantly less prevalent among survivors (55% vs. 71%, P<0.001). Key predictors of mortality included older age, beta-blocker use, prior stroke, lower serum haemoglobin levels, and elevated potassium and NT-proBNP levels. Each 10mL/min/1.73m2 decrease in eGFR was associated with a 1.22 (95% CI: 1.10-1.35, P<0.001) increase in mortality hazard. Additionally, a 1-year decline of 10mL/min/1.73m2 in eGFR resulted in a mortality hazard of 1.97 (95% CI: 1.45-2.69, P<0.001). CKD is prevalent in a real-world HF population and is an independent predictor of mortality. The current eGFR value and the eGFR slope from the previous year have the potential to be used for assessing individual mortality risk in the clinical follow-up of HF patients.

Targeted metabolomics identified novel metabolites, predominantly phosphatidylcholines and docosahexaenoic acid-containing lipids, predictive of incident chronic kidney disease in middle-to-elderly-aged Chinese adults

BackgroundEvidence is limited regarding the association of circulating metabolites with decline of kidney function, letting alone their value in prediction of development of chronic kidney disease (CKD). MethodsThis study included 3802 participants aged 64.1 ± 7.4 years from the Dongfeng-Tongji cohort, among whom 3327 were CKD-free at baseline (estimated glomerular filtration rate [eGFR] > 60 ml/min per 1.73 m2). We measured baseline levels of 211 metabolites with liquid chromatography coupled with mass spectrometry, including 25 amino acids, 12 acyl-carnitines, 161 lipids, and 13 other metabolites. ResultsThe mean (SD) absolute annual change in eGFR was −0.14 ± 4.11 ml/min per 1.73 m2 per year, and a total of 472 participants who were free of CKD at baseline developed incident CKD during follow-up of 4.6 ± 0.2 years (14.2 %). We identified a total of 22 metabolites associated with annual eGFR change and survived Bonferroni correction for multiple testing, including seven metabolites associated with eGFR increase (six being docosahexaenoic acid [DHA]-containing lipids) and 15 associated with eGFR decline (nine being phosphatidylcholines [PCs]). Among them, eight metabolites obtained non-zero coefficients in least absolute shrinkage and selection operator (LASSO) regression on incident CKD, indicating predictive potential, including one amino acid (arginine), one acyl-carnitine (C2), one lysophosphatidylcholine (LPC 22:6), two PCs (32:1 and 34:3), one triacylglycerol (TAG 56:8 [22:6]) and two other metabolites (inosine, niacinamide), and the composite score of these eight metabolites showed an odds ratio (OR) of 8.79 (95 % confidence interval [CI]: 7.49, 10.32; P < 0.001) per SD increase in association with incident CKD. The addition of the metabolite score increased the c-statistic of the reference model of traditional risk factors (including baseline eGFR) by 0.065 (95 % CI: 0.046 to 0.084; P = 3.39 × 10−11) to 0.765 (0.742 to 0.788) in 1000 repetitions of 10-fold cross-validation, while the application of two advanced machine learning algorithms, random forest (RF), and extreme gradient boosting (XGBoost) models produced similar c-statistics, to 0.753 (0.729 to 0.777) and 0.778 (0.733 to 0.824) with increases of 0.074 (0.055 to 0.093; P = 4.11 × 10−14) and 0.073 (0.032 to 0.114; P = 4.00 × 10−4), respectively. ConclusionsIn this study, we identified 22 metabolites associated with longitudinal eGFR change, nine of which were PCs and six were DHA-containing lipids. We screened out a panel of eight metabolites which improved prediction for the development of CKD by 9 % beyond traditional risk factors including baseline eGFR. Our findings highlighted involvement of lipid metabolism in kidney function impairment, and provided novel predictors for CKD risk.

Urinary Dickkopf-3 as a Potential Marker for Estimated Glomerular Filtration Rate Decline in Patients With Heart Failure.

Patients with chronic heart failure (HF) show an increased risk for the occurrence of chronic kidney disease and cardiorenal syndrome. Urinary Dickkopf-3 (uDKK3), a stress-induced, tubular profibrotic glycoprotein, may be elevated in HF as early as in New York Heart Association class I HF and may indicate subsequent decline in estimated glomerular filtration rate (eGFR). uDKK3 levels in patients with HF and controls were measured by enzyme-linked immunosorbent assay. eGFR was determined up to 5 years in HF. Change in eGFR was assessed with respect to baseline uDKK3 using (mixed-effect) linear and logistic regression models. A total of 488 patients with chronic HF and 45 control patients were included. Patients with HF showed higher median uDKK3 levels than controls (259.6 pg/mg creatinine [interquartile range (IQR), 119.2-509.4 pg/mg creatinine] versus 107.5 pg/mg creatinine [IQR, 60.5-181.2 pg/mg creatinine], P<0.001). Regression models demonstrated a significant association between log uDKK3 and the decline in eGFR during a median of 13 months (IQR, 12-59 months) (estimated higher eGFR loss, 0.8039 mL/min per 1.73 m2/year [95% CI, 0.002-1.606 mL/min per 1.73 m2/year], P=0.049; odds ratio, 1.345 [95% CI, 1.049-1.741], P=0.021). uDKK3 levels ≥354 pg/mg creatinine were associated with a significantly higher risk for eGFR decline at 1-year follow-up (estimated higher eGFR loss, 4.538 mL/min per 1.73 m2 [95% CI, 1.482-9.593 mL/min per 1.73 m2]), P=0.004). Even patients with HF without chronic kidney disease (n=334) had higher uDKK3 levels compared with controls (233.4 [IQR, 109.0-436.9 pg/mg creatinine] versus 107.5 [IQR, 60.5-181.2 pg/mg creatinine], P<0.001). The present findings indicate that uDKK3 is a promising prognostic biomarker for subsequent eGFR decline in patients with HF, irrespective of the presence of chronic kidney disease and even in the early stages of HF. This potential allows for early intervention to mitigate the deterioration of kidney function. Further investigation is warranted to validate its clinical utility.

Development and evaluation of a kidney health questionnaire and estimates of chronic kidney disease prevalence in the Cooperative Health Research in South Tyrol (CHRIS) study.

Kidney diseases are a public health burden but are poorly investigated in the general population. In light of inadequate survey tools, we developed a novel questionnaire for use in population-based studies, to retrospectively assess kidney diseases. The questionnaire covered general kidney diseases, reduced kidney function, and renal surgeries. It was administered between 2011 and 2018 to 11,684 participants (median age = 45 years) of the Cooperative Health Research in South Tyrol (CHRIS) study. Fasting estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were measured. By factor analysis we contextualized the questionnaire content with respect to thebiochemical measurements. We estimated overall and sex-stratified prevalence of kidney diseases, including possible CKD, calibrating them to the general target population via relative sampling weights. Population-representative prevalence of glomerulonephritis, pyelonephritis, and congenital kidney diseases was 1.0%, 3.0%, and 0.2%, respectively, with corresponding odds ratios for females versus males of 1.4 (95% confidence interval: 1.0, 2.0), 8.7 (6.2, 12.3), and 0.7 (0.3, 1.6), respectively. Prevalence of kidney dysfunction (eGFR < 60mL/min/1.73m2 or UACR > 30mg/g) was 8.59%, while prevalence of self-reported CKD was 0.69%, indicating 95.3% oflack of disease awareness, with a similar figure in people with diabetes or hypertension. Overall, 15.76% of the population was affected by a kidney disease of any kind. In the Val Venosta/Vinschgau alpine district, CKD prevalence aligned with Western European estimates. Kidney health questionnaire implementation in population studies is feasible and valuable to assess CKD awareness, which we found to be dramatically low.

Kidney physiopathologic changes in diabetic Golden-Syrian hamsters (Mesocricetus auratus) fed with hypercaloric diet

Diabetic nephropathy is the single major cause of end stage renal failure. The increase of visceral adipose tissue may lead to glomerular hypertrophy and chronic kidney disease. The objective is to determine renal changes in diabetic Golden-Syrian Hamster (Mesocricetus auratus) supplemented with a hypercaloric diet. Methods: One group of animals (n=10) was fed with a standard diet (SD), and the other group (n=10) was fed with a hypercaloric diet (HCD) for 1 month. Afterwards, both groups were treated with three doses of Streptozotocin. Hyperglycemia was determined throughout 73 days. The animal’s weight, blood and kidney tissues were obtained for analysis. Results: Diabetic animals fed with HCD diet manifested hyperglycemia (250-350 mg/dL) with significant weight loss (40g) and important glomerular filtration rate decrement (0.491mL/min). Regarding to renal fibrosis, all animals showed an increase of glomerular, interstitial, and cortical extracellular matrix (36.3, 75.2 and 70.7%, respectively). Diabetic animals that were SD-fed showed only mild hyperglycemia and slight increase of glomerular, interstitial, and cortical extracellular matrix. A group of animals (n=5) that was fed exclusively with HCD was also included in the study. Conclusions: Our finding suggests that HCD fed can accelerate the progression of chronic kidney disease in a diabetic condition.

Serum Concentration of Antidepressant Drugs in Geriatric Day Care Patients With Renal Insufficiency and Multimorbidity.

Geriatric depression is challenging to treat owing to age-related changes in pharmacokinetics and comorbidities. Although renal insufficiency and multimorbidity are typical geriatric complications that cannot be completely separated from each other, no study has examined the influence of these factors on the serum concentrations of antidepressants. For the first time, we evaluated the effects of these factors in combination on the dose-corrected serum concentration (C/D) of antidepressants in geriatric patients. In this retrospective study, data from 123 geriatric patients in a gerontopsychiatric day care unit at the University Hospital of Würzburg were analyzed. Multiple linear regression analysis and analysis of variance with confounders were used to examine the associations between glomerular filtration rate (GFR) and stages of renal impairment and the C/D of venlafaxine, mirtazapine, sertraline, and escitalopram corrected for multimorbidity, sex, lithium intake, and the number of triple whammy drugs. GFR (P < 0.001, ß = -0.070) was associated with the C/D of the active moiety of venlafaxine (N = 32). GFR, multimorbidity, and sex were not associated with the C/D of mirtazapine, escitalopram, or sertraline. As the influence of sex may be less pronounced than that of decreasing GFR in terms of the C/D of the active moiety of venlafaxine in geriatric patients, we recommend considering the GFR for dose adjustment rather than sex. In conclusion, even in patients with mild renal impairment, serum venlafaxine concentration should be monitored to prevent overdosing. Mirtazapine, sertraline, and escitalopram may be well-suited antidepressants for geriatric patients with renal function impairment stage 2-3 as well as multimorbidity.