Calcinosis Universalis Secondary to Silicone Injections in a Patient With HIV and Chronic Kidney Disease: A Case Report of Silicone-Induced Hypercalcemia.

Medical literature has long reported evidence of complications associated with cosmetic procedures, including silicone injections. Recent years have seen an increase in case reports involving hypercalcemia resulting from these injections. A common current hypothesis for the development of hypercalcemia associated with silicone injections is granulomatous inflammation against a foreign body.  This report aimed to describe the case of a 44-year-old African American male with human immunodeficiency virus (HIV) and chronic kidney disease (CKD) who presented to our hospital and was diagnosed with calcinosis universalis secondary to a history of silicone injections, as well as to present a literature review of silicone-induced hypercalcemia. This was a case report (n=1) from a large academic medical center for which the patient, who first presented in May 2023, had two inpatient admissions and two outpatient visits before being lost to follow-up. Relevant images, laboratory results, and treatments were included.  The patient's history was significant for HIV, hypertension, CKD, recurrent nephrolithiasis, and tobacco use disorder. Physical examination was positive for flank pain while labs were significant for Na 137 mmol/L, K 2.7 mmol/L, blood urea nitrogen (BUN) 28 mg/dL, creatinine 3.72 mg/dL, calcium 13.4 mg/dL, hemoglobin 9.3 g/dL, white blood cell count 6,700 u/L and platelet count 105,000 u/L. Renal ultrasound revealed bilateral nephrolithiasis and left-sided hydronephrosis. Computerized tomography (CT) upon admission showed hyperlucid deposits in the bilateral gluteal area. Initial management included intravenous (IV) fluids and one dose of IV pamidronate, which resulted in reduced calcium levels during the admission. Subsequent management included outpatient follow-up with endocrinology during which denosumab was prescribed. This case had similar findings to other reports in the literature detailing silicone-induced hypercalcemia, which also reported abnormal imaging or nephrolithiasis, low-normal parathyroid hormone (PTH), normal 25-hydroxyvitamin D, and elevated 1,25-dihydroxyvitamin D. Silicone injection-induced hypercalcemia should be considered as a differential diagnosis in patients presenting with otherwise unexplained elevated serum calcium and a history of past cosmetic procedures. If suspected, the use of imaging techniques (e.g. positron emission tomography (PET) scans or MRI) may help ascertain the diagnosis. Further research is needed to determine the most appropriate therapies for complex patients such as those with immunodeficiency or renal disease.

Finerenone's Impact on Major Adverse Cardiovascular Events in Chronic Kidney Disease and Type 2 Diabetes Mellitus: A Systematic Review.

Chronic kidney disease (CKD) impacts about 10% of adults globally and substantially elevates the risk of major adverse cardiovascular events (MACE), such as heart attacks, strokes, cardiovascular-related deaths, and hospital admissions due to heart failure. The interplay between CKD and cardiovascular disease (CVD) leads to poor health outcomes. Nevertheless, there is a scarcity of systematic reviews focusing on the effectiveness of finerenone, a new non-steroidal mineralocorticoid receptor antagonist (MRA), in lowering these risks. In this systematic review, we aim to evaluate the impact of finerenone on reducing MACE in individuals with CKD and type 2 diabetes mellitus (T2DM). CKD pathophysiology involves hyperglycemia, hypertension, and dyslipidemia, leading to glomerular hyperfiltration, inflammation, and fibrosis. Traditional treatments, including angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i), often fall short in preventing cardiovascular events. Steroidal MRAs like spironolactone and eplerenone, while effective in reducing proteinuria, are limited by hyperkalemia risks. Finerenone offers a more selective mechanism, reducing sodium retention, inflammation, and fibrosis, with a lower risk of hyperkalemia. We searched five electronic databases comprehensively, identifying studies consistently demonstrating that finerenone significantly reduces MACE and improves renal outcomes by reducing albuminuria and slowing the fall in estimated glomerular filtration rate (eGFR). However, limitations include study heterogeneity, short follow-up periods, and potential publication bias. In conclusion, finerenone shows promise as a therapeutic option for CKD and T2DM, reducing MACE and improving renal outcomes. Further research is needed to understand its long-term benefits and safety across diverse populations.

Insights of Fabry disease: Expert consensus approach for screening, diagnosis, and multidisciplinary management in chronic kidney disease.

The prevalence of Fabry disease (FD) among males with chronic kidney disease (CKD) of unknown etiology in Taiwan is 0.6%. Despite this, FD is frequently overlooked in clinical settings. To address this issue, two consensus meetings were conducted in Taiwan-one in August 2022 and another in April 2023. The first meeting established screening criteria based on age, gender, family history, cardiac involvement, and symptoms. The second meeting, with a multidisciplinary team, developed treatment recommendations. The consensus emphasizes the importance of proactive data collection in dialysis units and outpatient follow-ups to enhance FD detection and management. The screening algorithm recommends incorporating FD screening into the diagnostic process for CKD patients, regardless of age. Priority is given to patients with a family history of FD, early stroke history, or classical FD symptoms. Comprehensive screening is also advised for CKD patients without obvious classical symptoms. Screening protocols for males include measuring α-galactosidase A enzyme activity, with reduced activity leading to further tests such as lyso-Gb3 level quantification and genetic analysis. For females, the protocol involves evaluating lyso-Gb3 plasma levels and genetic testing. FD, though often underestimated, is more prevalent than recognized and necessitates a multidisciplinary approach for timely diagnosis. Enhancing awareness and adopting a comprehensive approach are essential for improving patient outcomes.

Kocuria rosea Sepsis in an Immunocompromised Patient: A Case Report.

Kocuria species, classified within the phylum Actinomycetota, class Actinomycetes, order Micrococcales, family Micrococcaceae, are Gram-positive coccoid bacteria. They bear morphological resemblance to Staphylococci spp and Micrococci spp, which often leads to misidentification and oversight as contaminants, given their presence as normal flora on human and animal skin and mucous membranes. Accurate identification of these organisms typically relies on automated systems such as MALDI-TOF-MS, Vitek-2 System, and 16S rRNA studies. Once considered rare, there is increasing recognition of Kocuria spp due to its emerging involvement in human infections. With increasing reports of infections associated with these bacteria, it is essential for clinical microbiologists to analyze and document the properties of the organism. This will aid clinicians in enhancing patient care and management. We present the case of a 53-year-old male patient with a complex medical history, including end-stage renal disease on maintenance hemodialysis, anemia of chronic disease, type 2 diabetes mellitus, and a history of rheumatic heart disease status post mitral valve replacement. This patient developed Kocuria rosea sepsis secondary to a central line catheter infection, highlighting the emerging clinical significance of Kocuria species in immunocompromised individuals.

A Case of Severe Acute Kidney Injury Due to an Antibiotic-Loaded Cement Spacer for Infected Knee Arthroplasty.

The treatment for periprosthetic joint infection frequently involves the placement of a high-dose antibiotic-loaded bone cement spacer (ALCS) into the debrided joint. Typical antibiotics in the spacer include aminoglycosides and vancomycin. It has been believed that systemic absorption of intraarticular antibiotics would be low and early experience suggested that the risk of acute kidney injury (AKI) from ALCS was minimal. However, recent case reports and case series have suggested a risk of acute kidney injury due to antibiotic absorption, though confounding factors are common. We report a case of severe AKI requiring hemodialysis with extremely high systemic tobramycin levels after the placement of an ALCS with increased dosing of antibiotics after previous failure to resolve a periprosthetic joint infection with a prior ALCS. There was no concomitant use of intravenous nephrotoxic antibiotics nor other confounding factors. Despite dialysis, the patient needed urgent removal of the ALCS to control tobramycin levels with subsequent resolution of the AKI. This case highlights the potentially serious nephrotoxicity of ALCS's, the importance of antibiotic type and dosing, and the value of close monitoring after ALCS placement, especially in a patient with chronic kidney disease.

Analysis of brominated flame retardants exposure-associated chronic kidney disease risk in the US population from the NHANES.

BACKGROUND: Exposure to brominated flame retardants (BFRs) may contribute the advancement of chronic kidney disease (CKD). The objective is to evaluate the renal effects of BFRs in patients with CKD. METHODS: Totally 7235 US participants of whom 1187 (16.41 %) were diagnosed with CKD were screened for this investigation from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016. The isotope dilution gas chromatography high-resolution mass spectrometry (GC/IDHRMS) was employed for identification of 11 polybrominated diphenyl ethers (PBDEs) and PBB153 serving as the exposure factor. A set of covariates concerning basic characteristics, renal function indicators and suffering from diseases of these participants was considered as potential confounding factors. Subgroup analyses to examine the impact of age and gender on the relationship between serum BFRs and CKD, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN). Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analyses were applied to identify relationship of individual BFRs and other anthropometric indicators in CKD. RESULTS: After adjusting for available confounding factors, PBDE100, PBDE28, PBDE85, PBDE47, PBDE99, and PBDE154 were positively correlated with CKD. PBDE28, PBDE66, PBDE47, PBDE183, PBDE100, PBDE99, PBDE85, PBDE154, and PBB153 were significantly negatively correlated with eGFR. PBDE66 and PBDE183 were positively correlated with UACR. PBDE28, PBDE17, PBDE66, PBDE100, PBDE47, PBDE85, PBDE154, PBDE99, PBDE183 and PBB153 were positively correlated with Scr. PBDE17, PBDE28, PBDE154, PBDE66, PBDE47, PBDE99, and PBDE209 were negatively associated with BUN. PBB153 was positively correlated with BUN. The subgroup results gender and age are key factors affecting the relationship of PBDEs and renal function indicators. Both WQS and QGS analyses revealed that exposure to mixed BFR was negatively correlated with eGFR and BUN, of which PBB153 and PBDE66 contributed the most, respectively, as well as positively correlated with Scr, in which PBDE66 contributed the most. CONCLUSION: Specific BFRs exposure was significantly correlated with renal function indicators, enhancing the potential risk of CKD. This pioneer investigation shed light on an overlooked impact of BFR exposure on CKD in US.

The Pattern of Practice in the Management of Early Diabetic Kidney Disease.

Background and objectives Diabetes is a leading cause of kidney failure in various regions worldwide. To detect renal disease in individuals with diabetes, screening typically involves evaluating the glomerular filtration rate and measuring albuminuria. Although there are established guidelines for these screenings, adherence to them varies. This study aims to examine the prevalence of albuminuria screening among adults with diabetes mellitus (DM) and to assess the different practices in managing these patients across primary and tertiary care settings. Methods This cross-sectional observational study involved adult patients with DM attending outpatient clinics in both primary and tertiary care settings. Patient data were gathered using a standardized form, excluding those with established chronic kidney disease (CKD) who were under nephrology care. Results The study included 1,010 patients, with 303 (30%) from primary care clinics and 707 (70%) from tertiary care clinics. The cohort comprised 582 (58%) females, with a median age of 62 years (IQR: 55-70), and approximately 990 (98%) had type 2 DM (T2DM). Annual albumin-to-creatinine ratio (ACR) screening was conducted for 498 out of 1,010 patients (49%) (95% confidence interval {CI}: 46%-52%). Screening compliance was notably higher in primary care settings compared to tertiary care clinics. Older patients (over 60 years) and those with hypertension or cardiac conditions were less likely to undergo screening. Among those screened, 185 of 498 patients (37%) (95% CI: 33%-41%) had abnormal albuminuria (ACR > 3). Conclusion Albuminuria is a significant indicator of progressing renal disease and cardiovascular risk. The annual screening rate for albuminuria in diabetic patients is inadequate. Primary care physicians show better adherence to screening guidelines compared to their tertiary care counterparts. Increasing physician awareness about the importance of screening could improve guideline compliance and mitigate the adverse effects of albuminuria.

Associations between multi-metal joint exposure and decreased estimated glomerular filtration rate (eGFR) in solar greenhouse workers: A study of a unique farmer group.

BACKGROUND: Solar greenhouse workers, a unique farmer group, have been reported to have a higher risk of chronic kidney disease (CKD) compared to the general population, possible due to exposure to multiple metals. OBJECTIVE: This study aimed to investigate the associations between exposure to multiple metals and the estimated glomerular filtration rate (eGFR). METHODS: A cross-sectional study was conducted in the Northwest China. Urine samples were tested for concentration of 14 metals, including chromium, manganese, iron et al. Blood creatinine was measured to calculate eGFR, which was to evaluate the kidney function. Linear model and the Bayesian Kernel Machine Regression (BKMR) models were used to evaluate the associations between metals exposure and eGFR. RESULT: The study included 281 solar greenhouse workers, with 128 (45.6%) males and 153 (54.4%) females. The highest median concentrations of metals were zinc (418.55 µg/L), strontium (368.77 µg/L), and iron (55.73 µg/L), respectively. The linear model analysis showed that urinary levels of copper and zinc were negatively associated with eGFR [ß = -0.021, 95% CI (-0.048, -0.007); ß = -0.018, 95% CI (-0.068, -0.005)] considering a false discovery rate. BKMR results indicated a significant overall negative effect of 14 metals exposure on the eGFR when all metal levels were above the 50th percentile compared to the median value. CONCLUSIONS: The decrease in eGFR among solar greenhouse workers was related to mixed metal exposure. Reducing exposure to the metals of copper, zinc, and lead could effectively protects kidney function. Further prospective studies are needed to resolve concerns about reverse causality.

Optimization of double-cooking condition for low potassium potatoes using response surface methodology (RSM).

This study aimed to establish optimal double-cooking condition using response surface methodology that maintained hardness while maximizing potassium reduction rate. The experimental design was based on the first cooking time (4.5-5.5 min) and rinsing time (20-60 s) through central composite design. This study suggested an optimal double-cooking condition of 5.5 min for first cooking and 57.57 s for rinsing. The model corroborated that the double-cooking condition significantly influenced dependent variables, including potassium reduction rate, hardness, and color (b-value). As the first cooking time increased, the potassium reduction rate increased and the hardness and b-value decreased. SEM revealed that double-cooked potato had more organized and netted structure. This structure could be helpful to maintain hardness, but relatively large amount of potassium could be leached out. The established optimal double-cooking condition for potatoes holds promise for broadening the dietary options for chronic kidney disease patients.

Dialysis Disequilibrium Syndrome With Cerebral Edema in an Adult Patient Following the Initial Dialysis Session.

Dialysis is a common treatment for removing toxins, electrolytes, and excess fluids due to impaired kidney function. A rare but life-threatening complication that can arise is dialysis disequilibrium syndrome (DDS) with cerebral edema. DDS is characterized by a range of neurological symptoms that may occur following dialysis. Its incidence is not well-established because it often presents with nonspecific symptoms, making diagnosis challenging. Here, we present a case of a 64-year-old female with a history of hypertension and chronic kidney disease stage 5, who sought evaluation for nausea and vomiting with coffee-ground emesis that began three weeks prior. Despite an initial blood transfusion stabilizing her hemoglobin with no further hematemesis, she developed DDS with cerebral edema after her first dialysis session. The condition was managed with 3% hypertonic saline, which quickly resolved both her cerebral edema and neurological symptoms. She tolerated subsequent dialysis sessions without complications and was discharged with a follow-up arranged with nephrology and an outpatient dialysis chair. This case report reviews the clinical features, risk factors, pathophysiology, management, and treatment goals for DDS. In patients commencing dialysis, particular attention should be given to preventing DDS, especially in those with elevated blood urea nitrogen levels above 100 mg/dL. Prompt recognition and treatment are crucial to balance the osmotic gradient and prevent severe outcomes, such as cerebral edema and death.

Nutritional profile and infection-related hospital admissions in children with chronic kidney disease.

BACKGROUND: Protein energy wasting (PEW) and undernutrition are highly prevalent in children with chronic kidney disease (CKD), but their impact on clinical outcomes is not well described. This prospective longitudinal study in children with CKD assessed the association of nutritional parameters with infection-related hospital admissions (IRHA). METHODS: Children with CKD2-5D aged 2-18 years and infection-free for 1 month were recruited over 5 years. Evaluation for undernutrition by subjective global nutritional assessment and for PEW using paediatric criteria was undertaken and categorized as mild (>2 criteria), standard (>3 criteria) and modified PEW (>3 criteria with short stature). The IRHA (severe viral, bacterial or fungal infections) were recorded. RESULTS: Among 137 children (45 on dialysis; age 123 ± 46 months; 70% males), undernutrition was seen in 60% and PEW in 52%. In over 38 ± 21 months follow-up, 107 (78%) required hospital admissions (67% IRHA). The incidence rate of IRHA in days per patient-year was higher in those with undernutrition compared to well-nourished children [1.74 (1.27, 2.31) vs. 0.65 (0.44, 0.92) p < 0.0001] and higher in those with PEW compared to no PEW [1.74 (1.30, 2.28) vs. 0.56 (0.36, 0.82) p < 0.0001] respectively. On adjusted analysis, independent risk factors for IRHA were undernutrition, low BMI, hypoalbuminemia and dialysis status with modified PEW [OR 5.34 (2.16, 13.1) p < 0.001] and raised CRP [OR 4.66 (1.56, 13.9) p = 0.006] having the highest risk. Additionally, modified PEW and BMI were noted to have a twofold risk for recurrent infections. CONCLUSION: In children with CKD2-5D, incidence rate of IRHA was significantly higher in those with undernutrition and PEW. While dialysis, poor nutritional status and inflammation were risk factors for IRHA, modified PEW and BMI were associated with recurrent infections.

The Efficacy and Safety of Probiotic Combinations Lobun Forte® Versus Renadyl® in Patients With Chronic Kidney Disease: A Comparative, Phase IV, Randomized, Open-Label, Active-Controlled, Parallel Study.

BACKGROUND: Chronic kidney disease (CKD) often leads to gut microbiota imbalance, accelerating disease progression and increasing uremic toxins and inflammation. We conducted a randomized clinical trial comparing outcomes between two multi-strain probiotic supplements Lobun Forte® (Sanzyme P Ltd, Hyderabad, India) containing Streptococcus thermophilus, Lactobacillus acidophilus, Bifidobacterium longum, and Bacillus coagulans and Renadyl® (Kibow Biotech, LLC., Pennsylvania, United States) containing S. thermophilus, L. acidophilus, and B. longum. MATERIALS AND METHODS: Sixty patients with stage 3-4 CKD were randomized to receive either Lobun Forte (n=30) or Renadyl (n=30) for six months, with each supplement providing 45 billion CFU/capsule, twice daily. Primary outcomes included quality of life (QoL) (Short-Form 8 (SF-8) score), reductions in uremic toxins (p-cresyl sulfate (PCS), 3-indoxyl sulfate (IS), indole-3-acetic acid (IAA)), blood urea nitrogen (BUN), serum creatinine, and serum uric acid. Secondary outcomes assessed oxidative stress, inflammatory biomarkers, and estimated glomerular filtration rate (eGFR). Results: Both Lobun Forte and Renadyl groups showed significant improvements in QoL, with Lobun Forte achieving a 53.5% improvement (16.43 point increase) and Renadyl a 51.1% improvement (15.27 point increase) in SF-8 scores (p < 0.0001). The levels of IS decreased significantly in both groups (p < 0.0001), with Lobun Forte reducing IS by 29.72% and Renadyl by 24.20%. In terms of other uremic toxins, Lobun Forte showed non-significant (p > 0.05) reductions in mean PCS (7.63%) and IAA (15.57%), whereas Renadyl demonstrated a significant (p = 0.0314) decrease in PCS (20.75%) and a non-significant (p > 0.05) reduction in IAA (12.35%). Both groups showed significant (p < 0.0001) reductions in BUN and serum creatinine levels. Serum uric acid levels showed a significant (p = 0.0448) reduction with Lobun Forte while Renadyl exhibited a non-significant reduction (p = 0.1034). Lobun Forte significantly (p = 0.0359) reduced mean high-sensitivity C-reactive protein (hsCRP) levels, while Renadyl showed a non-significant reduction (p = 0.0876). Both groups had non-significant reductions in interleukin-6 and tumor necrosis factor-alpha levels (p > 0.05). Further, both groups experienced significant (p < 0.0001) increases in mean glutathione levels and nitric oxide levels. Additionally, Renadyl resulted in a significant reduction in mean malondialdehyde, whereas Lobun Forte showed a non-significant reduction. Both probiotics significantly (p < 0.0001) improved eGFR, with Lobun Forte increasing it by 40.4% and Renadyl by 36.9%. Both probiotics were well tolerated, with a favorable safety profile throughout the study. Conclusion: Both Lobun Forte and Renadyl effectively improve the quality of life in patients with stage 3-4 CKD by modulation of uremic toxins, renal parameters, inflammatory biomarkers, oxidative biomarkers, and eGFR. These findings suggest that both probiotics may help delay CKD progression by modulating the gut-kidney axis.

Reversal of heavy arterial calcification in a rat model of chronic kidney disease using targeted ethylene diamine tetraacetic acid-loaded albumin nanoparticles.

Background: Elastin degradation and severe calcification in the medial layer of the vessel wall, known as medial arterial calcification (MAC), is typical in the aging population and patients with metabolic disorders, such as diabetes and chronic kidney disease (CKD). We have previously reported that ethylene diamine tetraacetic acid (EDTA) delivery to the site of calcification can be achieved by tagging nanoparticles with an elastin antibody that recognizes explicitly damaged elastin, and such systemic therapy can remove focal calcium deposits from the calcified arteries in CKD rodent model. The current study aims to test whether heavy calcification seen throughout arterial tree and kidneys in CKD can be reversed with nanoparticle therapy. Methods: Thirty healthy male Sprague-Dawley rats weighing approximately 300 g, were placed on an adenine diet for 21 non-consecutive days to induce kidney failure, followed by daily vitamin D3 (VitD3) injections for 4 sequential days to cause severe calcification throughout the cardiovascular system and kidneys. DiR-dye loaded and elastin antibody conjugated albumin nanoparticles were used to confirm the targeting of nanoparticles to the calcification area. The rats were divided into two groups for targeted removal of calcification starting at day 7 of the last doses of VitD3. The experimental group received biweekly IV injections of anti-elastin antibody conjugated EDTA loaded human serum albumin nanoparticles (EDTA-HSA-El-Ab NPs), while the sham controls received blank nanoparticles (Blank-HSA-El-Ab NPs) (5 injections in total). Micro-computed tomography (microCT) was used to analyze the extent of calcification. Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry studies were performed for osteogenic markers, including bone morphogenic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), and tissue non-specific alkaline phosphatase (TNAP). For comparison, aortic ring organ cultures from healthy rats were treated with high phosphate to induce calcification in vitro, and then they were treated with EDTA. Human calcified femoral arteries were also treated ex vivo with EDTA-HSA-EL-Ab NPs to test if nanoparticles remove heavy calcification. Results: EDTA-loaded nanoparticles that specifically target degraded elastin reversed existing heavy mineral deposits in arteries, as per elemental calcium analysis (124.161±34.410 µg Ca per mg of the dry aorta in Blank-HSA-El-Ab NPs vs. 100.520±19.131 µg in EDTA-HSA-El-Ab NPs group, P=0.04) and microCT (object volume, 129.001±37.785 vs. 29.815±24.169 mm3, P=0.0005). The reversal of aortic calcification was accompanied by a significant reduction of bone-associated mRNA expression of BMP2 and RUNX2 (P=0.01). Immunohistochemistry studies corroborated RT-PCR results, showing a reduction of BMP2 and RUNX2 stains in the vessel wall. The rat aortic ring culture study also showed similar results, where osteogenic genes (BMP2, RUNX2) and proteins (BMP2, RUNX2, TNAP) were suppressed upon reversal of calcification with EDTA (P=0.001). We also show ex vivo reversal of human femoral artery calcification by microCT (calcium intensity: untreated, 57.721±28.551 vs. day 6 of treatment, 5.441±3.615, P=0.01) by EDTA nanoparticle therapy. Conclusions: This is the first study showing the removal of calcium from heavily calcified arteries by using intravenous targeted EDTA therapy. Such therapy also reversed vascular smooth muscle cell osteoblastic transition and apoptosis in the arterial tissue, thereby potentially creating an environment for suitable tissue repair.

A rare multisystemic disorder with chronic kidney disease: Karyomegalic interstitial nephritis due to homozygous FAN1 c.2260C>T variant.

Karyomegalic interstitial nephritis (KIN) is a rare entity associated with biallelic FAN1 (FANCD2/FANCI-Associated Nuclease 1) gene variants. In FAN1-related KIN, abnormal liver function tests and respiratory involvement are common, in addition to chronic kidney disease. Karyomegalic changes have also been reported in many other organs in patients with FAN1-related KIN in various studies. We report the case of a 35-year-old male with chronic kidney disease of unknown aetiology, concurrent recurrent upper and lower respiratory tract infections, and elevated liver function test results with unidentified aetiology. The patient's family history was remarkable for consanguineous parent marriage and history of kidney transplantation in his aunt. A kidney biopsy was performed, which was consistent with KIN. Clinical exome sequencing revealed a homozygous nonsense variant NM_014967.5 (FAN1): c. 2260C > T (p.Arg754Ter). According to the American College of Medical Genetics (ACMG) criteria, this variant is pathogenic and, to the best of our knowledge, has not been previously reported, homozygously. Therefore, the histopathological and clinical diagnoses of KIN were confirmed by genetic studies in our patient. This case report expands the genetic spectrum of FAN1-related KIN, and briefly reviews the current literature data.

Long-Term Interplay Between SARS-CoV-2 and Renal Impairment.

Introduction The SARS-CoV-2 virus causes the highly contagious coronavirus disease 2019 (COVID-19), which most commonly manifests as severe acute respiratory syndrome. The virus is part of the Coronaroviridae family, a group of viruses that can cause various diseases, such as the common cold, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). The World Health Organization (WHO) declared the outbreak of COVID-19 as a pandemic on March 11, 2020. On February 26, 2020, Romania confirmed the first case of COVID-19, initiating a series of challenges that negatively impacted the lives of thousands of people. The COVID-19 pandemic has had a disproportionate effect on patients at risk of kidney damage. Patients with chronic kidney disease (CKD) are at high risk of SARS-CoV-2 infection and mortality associated with COVID-19. CKD is associated with pronounced immunodeficiency and represents a risk factor for contracting the infection, but also increases the risk of hospitalization, oxygen therapy, and prolonged treatments. The evidence regarding the management of patients with CKD undergoing renal replacement therapy (RRT) infected with SARS-CoV-2 is still misleading. While these are high-risk patients due to the presence of multiple comorbidities, especially cardiovascular, e.g., hypertension, left ventricular hypertrophy, but also diabetes, the question remains whether RRT itself is associated with a worse prognosis in patients infected with SARS-CoV-2, although infections generally induce severe complications in patients with CKD and RRT. Methods This retrospective study aims to analyze the evolution of COVID-19 disease in patients with CKD, focusing on the association with some common comorbidities such as ischemic coronary disease (ICD), obesity, and diabetes. The study included 72 hemodialyzed patients; they were hospitalized between November 2020 and February 2021 at "Sf. Ioan" Clinical Emergency Hospital, Nephrology and Dialysis Clinic; peritoneal dialysis patients were excluded. Results Older age was found to be an important risk factor for death in hemodialyzed patients admitted with COVID-19 infection. Obese patients were found to be at greater risk of mortality. Discussion This study showed that there is a complex relationship between COVID-19 infection and increased mortality in patients with CKD associating ischemic coronary disease, obesity, and diabetes.

Tofogliflozin attenuates renal lipid deposition and inflammation via PPARα upregulation mediated by miR-21a impairment in diet-induced steatohepatitic mice.

We previously demonstrated hepatic, cardiac, and skin inflammation in a high-fat diet-induced steatotic liver disease (SLD) model. However, the molecular mechanism in the kidneys in this model remains unclear. It has been recently reported that SGLT2 inhibitors improve chronic kidney disease (CKD). Therefore, we used this model to evaluate the effects of tofogliflozin on renal lipid metabolism and inflammation. Male 8-10-week-old C57Bl/6 mice were fed a high-fat/high-cholesterol/high-sucrose/bile acid (HF/HC/HS/BA) diet with 0.015% tofogliflozin (Tofo group) or an HF/HC/HS/BA diet alone (SLD group). After eight weeks, serum lipid profiles, histology, lipid content, and mRNA/microRNA and protein expression levels in the kidney were examined. The Tofo group showed significant reductions in body (26.9 ± 0.9 vs. 24.5 ± 1.0 g; p < 0.001) and kidney weight compared to those of the SLD group. Renal cholesterol (9.1 ± 1.6 vs. 7.5 ± 0.7 mg/g; p < 0.05) and non-esterified fatty acid (NEFA) (12.0 ± 3.0 vs. 8.4 ± 1.5 µEq/g; p < 0.01) were significantly decreased in the Tofo group. Transmission electron microscopy revealed the presence of fewer lipid droplets. mRNA sequencing analysis revealed that fatty acid metabolism-related genes were upregulated and NFκB signaling pathway-related genes were downregulated in the Tofo group. MicroRNA sequencing analysis indicated that miR-21a was downregulated and miR-204 was upregulated in the Tofo group. Notably, the expression of PPARα, which has been known to be negatively regulated by miR-21, was significantly increased, leading to enhancing ß-oxidation genes, Acox1 and Cpt1 in the Tofo group. Tofogliflozin decreased renal cholesterol and NEFA levels and improved inflammation through the regulation of PPARα and miR-21a.

Methotrexate Toxicity-Induced Pancytopenia and Mucocutaneous Ulcerations in Psoriasis.

Methotrexate (MTX) is a commonly used immunosuppressant and chemotherapeutic agent, widely prescribed for autoimmune diseases such as psoriasis, rheumatoid arthritis, and certain malignancies. It functions by inhibiting dihydrofolate reductase, leading to impaired DNA synthesis and cell proliferation. While generally well-tolerated, MTX has a narrow therapeutic index, and its adverse effects can be severe, including hepatotoxicity, pulmonary toxicity, and hematological complications such as pancytopenia. Pancytopenia involves the reduction of all three blood cell lines and can result in significant morbidity and mortality. The risk of MTX toxicity is notably higher in patients with renal impairment, as the kidneys are the primary route of drug excretion. Renal dysfunction can lead to the accumulation of MTX, enhancing its toxicity. Numerous studies and case reports have highlighted the risks of MTX toxicity, especially in patients with renal impairment. Pancytopenia can present insidiously, with symptoms such as mucosal ulcers, fever, and generalized weakness, making early detection crucial. We report a case of a male patient in his late 40s with a complex medical history, including psoriasis, insulin-dependent type 2 diabetes mellitus, chronic kidney disease (CKD) stage 3b, and coronary artery disease (CAD). The patient presented to the emergency department with a one-week history of fever, generalized weakness, mouth sores, and a five-day history of bilateral lower limb swelling and pain. Vital signs were stable, but physical examination revealed pallor, large ulcerative lesions in the buccal mucosa, and erythematous, scaly lesions on the lower limbs. The patient's medication history included methotrexate, which he had stopped two months prior but was inadvertently resumed at an increased dose two weeks prior to presentation. Laboratory findings revealed pancytopenia with worsening trends, prompting a bone marrow biopsy that showed hypocellular marrow. The patient's CKD likely exacerbated the MTX toxicity due to impaired drug clearance, leading to pancytopenia. Treatment included intravenous leucovorin, blood and platelet transfusions, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Despite initial critical presentation, the patient showed significant improvement, with recovery of blood counts and resolution of symptoms. He was discharged with stable hemoglobin, platelet, and white blood cell counts.

A PDE1 inhibitor, vinpocetine, ameliorates epithelial-mesenchymal transition and renal fibrosis in adenine-induced chronic kidney injury in rats by targeting the DNMT1/Klotho/ß-catenin/Snail 1 and MMP-7 pathways.

Tubulointerstitial fibrosis (TIF) is present with chronic kidney disease (CKD). Vinpocetine (Vinpo) is used for treating cerebrovascular deficits, exhibiting some kidney-beneficial effects; however, its role in TIF is uncertain. So, the aim of this study was to investigate its potential impact on adenine-induced fibrotic CKD and explore the underlying mechanistic aspects. Eighteen male Wistar rats were categorized into three groups (n = 6 each). Group I was kept as controls and given saline; group II received adenine (300 mg/kg, twice weekly, i.p.) for induction of the CKD model; and group III was administered Vinpo (20 mg/kg/d, orally) concurrently with adenine. All treatments were administered for 4 weeks. Vinpo revealed an improvement in renal function and an alleviation of inflammation triggered by adenine via diminishing serum tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels. Further, Vinpo repressed the epithelial-mesenchymal transition (EMT) with preserved E-cadherin mRNA expression and lowered gene and immune expression of fibronectin and vimentin, respectively, besides attenuating the elevated G2/M arrest-related molecules (renal Ki67 protein contents and p21 gene expression). Renal pathological alterations caused by adenine were attenuated upon Vinpo administration. Interestingly, Vinpo suppressed abnormal renal ß-catenin immunoreactivity, Snail 1, and MMP-7 gene expression while simultaneously restored Klotho protein expression by downregulating DNA methyltransferase 1 enzyme (DNMT1) protein expression in the kidney. These data indicated that Vinpo effectively mitigated EMT and G2/M arrest-induced renal fibrosis in adenine-induced CKD rats by targeting DNMT1-associated Klotho suppression, subsequently inhibiting ß-catenin and its fibrotic downstream genes.

Effects of soluble Klotho and Wnt/ß-catenin signaling pathway in vascular calcification in chronic kidney disease model rats and the intervention of Shenyuan granules.

OBJECTIVE: This study aimed to investigate the effect of the soluble Klotho (sKlotho)/Wnt/ß-catenin signaling pathway on vascular calcification in rat models of chronic kidney disease (CKD) and the intervention effect of Shenyuan granules. METHODS: Rats with 5/6 nephrectomy and high phosphorus feeding were used to establish the vascular calcification model. The rats were given gradient doses of Shenyuan granules aqueous solution and calcitriol solution by gavage for 8 weeks, which were divided into experimental group and positive control group. RESULTS: The 5/6 nephrectomy combined with high phosphorus feeding induced thoracic aortic calcification in rats. Shenyuan granules intervention increased the serum sKlotho level, inhibited the mRNA and protein expression of Wnt1, ß-catenin, and Runx2 in the thoracic aorta, and alleviated thoracic aortic media calcification in rats. CONCLUSION: Shenyuan granules may partially regulate the Wnt/ß-catenin signaling pathway via serum sKl to interfere with the expression of Runx2, thereby improving vascular calcification in CKD.