Changes in tubular biomarkers with dietary intervention and metformin in patients with autosomal dominant polycystic kidney disease: a post-hoc analysis of two clinical trials.

BACKGROUND: Tubular biomarkers, which reflect tubular dysfunction or injury, are associated with incident chronic kidney disease and kidney function decline. Several tubular biomarkers have also been implicated in the progression of autosomal dominant polycystic kidney disease (ADPKD). We evaluated changes in multiple tubular biomarkers in four groups of patients with ADPKD who participated in one of two clinical trials (metformin therapy and diet-induced weight loss), based on evidence suggesting that such interventions could reduce tubule injury. METHODS: 66 participants (26 M/40 F) with ADPKD and an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m2 who participated in either a metformin clinical trial (n = 22 metformin; n = 23 placebo) or dietary weight loss study (n = 10 daily caloric restriction [DCR]; n = 11 intermittent fasting [IMF]) were included in assessments of urinary tubular biomarkers (kidney injury molecule-1 [KIM-1], fatty-acid binding protein [FABP], interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and human cartilage glycoprotein-40 [YKL-40]; normalized to urine creatinine), at baseline and 12 months. The association of baseline tubular biomarkers with both baseline and change in height-adjusted total kidney volume (HtTKV; percent change from baseline to 12 months) and estimated glomerular filtration rate (eGFR; absolute change at 12 months vs. baseline), with covariate adjustment, was also assessed using multiple linear regression. RESULTS: Mean ± s.d. age was 48 ± 8 years, eGFR was 71 ± 16 ml/min/1.73m2, and baseline BMI was 30.5 ± 5.9 kg/m2. None of the tubular biomarkers changed with any intervention as compared to placebo. Additionally, baseline tubular biomarkers were not associated with either baseline or change in eGFR or HtTKV over 12 months, after adjustments for demographics, group assignment, and clinical characteristics. CONCLUSIONS: Tubular biomarkers did not change with dietary-induced weight loss or metformin, nor did they associate with kidney disease progression, in this cohort of patients with ADPKD.

The effect of vitamin D deficiency during pregnancy on adverse birth outcomes in neonates: a systematic review and meta-analysis.

Objective: To systematically evaluate the effect of vitamin D deficiency during pregnancy on neonatal adverse outcomes, such as preterm infants, low birth weight infants (LBWI), and small for gestational age (SGA) infants. Methods: A comprehensive literature search was conducted across multiple databases including PubMed, Embase, Cochrane Library, SinoMed, Wanfang Data Knowledge Service Platform, China National Knowledge Internet (CNKI), and VIP Chinese Science and Technology Journal Database (VIP). Following predefined inclusion and exclusion criteria, two researchers independently screened, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using RevMan 5.4 and Stata 14 software to synthesize the findings. Results: This study incorporated 13 cohort studies from 8 different countries and regions, encompassing a total of 55,162 pregnant women, among whom 28,155 were identified as having vitamin D deficiency. The Newcastle-Ottawa Scale (NOS) score ranged from 7-9 points. Meta-analysis results indicated a higher incidence of LBWI (OR = 5.52, 95% CI = 1.31-23.22. P = 0.02) in the group of pregnant women with vitamin D deficiency compared to those with adequate levels. However, there was no statistically significant difference in the likelihood of premature birth (OR = 1.25, 95% CI = 0.78-1.99. P = 0.36) or SGA (OR = 1.47, 95% CI = 0.81-2.68. P = 0.21) among newborns born to mothers with vitamin D deficiency vs. those with sufficient levels of vitamin D. Subgroup analysis based on the timing of maternal blood collection revealed that there was no statistically significant association between vitamin D levels during pregnancy and the incidence of preterm birth across all stages of pregnancy. Furthermore, vitamin D deficiency throughout the entire pregnancy was associated with an increased incidence of neonatal LBWI, whereas vitamin D levels during the first, second, and third trimesters did not demonstrate statistically differences on LBWI. Neonates born to mothers with vitamin D deficiency throughout pregnancy were found to have a higher likelihood of developing SGA. However, there was no statistically significant association between vitamin D levels and the development of SGA during the first and second trimesters. Conclusions: Adequate levels of vitamin D during pregnancy may decrease the incidence of LBWI, although further research is needed to determine its impact on the occurrence of preterm birth and SGA. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024535950, Identifier: (CRD42024535950).

Statin therapy in patients with early-stage autosomal dominant polycystic kidney disease: Design and baseline characteristics.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development and continued growth of multiple cysts in the kidneys leading to ultimate loss of kidney function in most patients. Currently, tolvaptan is the only agency approved therapy to slow kidney disease advancement in patients with faster progressing disease underscoring the need for additional ADPKD therapies suitable for all patients. We previously showed that pravastatin slowed kidney disease progression in children and young adults with ADPKD. However, the intervention has not been tested in an adult cohort. AIMS: The aim of the study is to conduct a single center, randomized, placebo-controlled double-blinded clinical trial to determine the efficacy of pravastatin on slowing kidney disease progression in adult patients with early stage ADPKD. METHODS: One hundred and fifty adult patients with ADPKD and eGFR ≥60 ml/min/1.73m2 will be enrolled in the study and randomized to receive 40 mg/day pravastatin or placebo for a period of 2-years. OUTCOMES: The primary outcome of the trial is change in total kidney volume assessed by magnetic resonance imaging (MRI). Secondary outcomes include change in kidney function by iothalamate GFR and renal blood flow and markers of inflammation and oxidative stress. CONCLUSION: This study will assess the kidney therapeutic benefits of pravastatin in adult patients with ADPKD. The recruitment goal of 150 subjects was attained and the study is ongoing. REGISTRATION: This study is registered on Clinicaltrials.gov # NCT03273413.