Denosumab Use in Chronic Kidney Disease Associated Osteoporosis: A Narrative Review.

Chronic kidney disease (CKD) and hemodialysis (HD) patients have a high incidence of bone disease and increased fracture risk, making effective management of their bone health a clinical challenge. Denosumab, a human monoclonal antibody, has been investigated as a therapeutic option in this patient population. In this review, we summarize the current evidence on the efficacy and safety of denosumab in CKD and HD patients. A comprehensive search of the relevant literature was conducted, including randomized controlled trials, observational studies, and meta-analyses. The findings suggest that denosumab reduces the risk of fractures and improves bone mineral density in all stages of CKD. The results of this review support the use of denosumab as a promising option for managing bone disease in CKD and HD patients.

Acute Focal Bacterial Nephritis in a Patient with Solitary Kidney: Case Report.

INTRODUCTION: Acute focal bacterial nephritis is an underdiagnosed condition. It clinically resembles acute pyelonephritis. If unrecognized and undertreated, it may progress into complications (kidney abscess and scars). Contrast-enhanced computed tomography (CT) reveals specific images of the disease and is considered the gold standard to make the diagnosis. CASE REPORT: A 63-year-old male patient with solitary kidney presented with symptoms compatible with acute pyelonephritis. Kidney ultrasound was not conclusive. Because of persisting high-grade fever not resolving after 48 hours of antibiotics, a contrast-enhanced CT was then performed, and the diagnosis of acute focal bacterial nephritis was made. A repeat CT after three weeks of intravenous (IV) antibiotics showed marked improvement of the intrarenal lesions, and a fourth week of IV antibiotics was dispensed. CONCLUSION: Diagnosing acute focal bacterial nephritis is important (particularly in a patient with solitary kidney). This will dictate the therapy duration. Unlike acute pyelonephritis, acute focal bacterial nephritis requires at least three weeks duration of antibiotics to avoid progress into further complications.

Improvement of Dialysis Dosing Using Big Data Analytics.

OBJECTIVES: Large amounts of healthcare data are now generated via patient health records, records of diagnosis and treatment, smart devices, and wearables. Extracting insights from such data can transform healthcare from a traditional, symptom-driven practice into precisely personalized medicine. Dialysis treatments generate a vast amount of data, with more than 100 parameters that must be regulated for ideal treatment outcomes. When complications occur, understanding electrolyte parameters and predicting their outcomes to deliver the optimal dialysis dosing for each patient is a challenge. This study focused on refining dialysis dosing by utilizing emerging data from the growing number of dialysis patients to improve patients' quality of life and well-being. METHODS: Exploratory data analysis and data prediction approaches were performed to gather insights from patients' vital electrolytes on how to improve the patients' dialysis dosing. Four predictive models were constructed to predict electrolyte levels through various dialysis parameters. RESULTS: The decision tree model showed excellent performance and more accurate results than the support vector machine, linear regression, and neural network models. CONCLUSIONS: The predictive models identified that pre-dialysis blood urea nitrogen, pre-weight, dry weight, anticoagulation, and sex had the most significant effects on electrolyte concentrations. Such models could fine-tune dialysis dosing levels for the growing number of dialysis patients to improve each patient's quality of life, life expectancy, and well-being, and to reduce costs, efforts, and time consumption for both patients and physicians. The study's results need to be validated on a larger scale.

The effects and safety of high dose vitamin D3 in hemodialysis patients.

Background: Different studies have shown that hemodialysis patients require higher doses of Vitamin D3 (VD3) than the general population to achieve satisfactory replenishment. This study aims to assess the safety of such practice and its benefits on some of the parameters of Chronic Kidney Disease- Mineral and Bone Disorder (CKD-MBD). Methods: A single-center clinical trial assessing the benefits of high dose VD3 in hemodialysis patients. The dose of VD3 (300,000 IU) was administered orally and monthly from April to December 2020 (9 months) at the dialysis unit. The data analyzed were blood levels of calcium, phosphorus, alkaline phosphatase, 25(OH)D, 1,25(OH)2D and intact parathyroid hormone (iPTH) done every three months. Results: We could recruit a cohort of 23 patients. Blood levels of 25(OH)D increased significantly in 82.6% of the patients to above 30 ng/ml. A similar effect was observed with 1, 25(OH)2D levels. iPTH levels decreased significantly when levels of 25(OH)D exceeded 30ng/ml at the end of the nine months. Vitamin D serum levels were typically measured immediately before the next monthly dose was administered. Blood levels of calcium, phosphorus, and alkaline phosphatase were stable during the study period. No events of hypercalcemia were reported, and no patient discontinued the monthly VD3 supplementation. Conclusion: Monthly administration of a high dose of VD3 over a long period of nine months in hemodialysis patients was found to be safe and beneficial in VD3 replenishment. It also allowed a significant decrease in iPTH levels. Further studies are warranted to identify the therapeutic target level of 25(OH)D in hemodialysis patients, allowing beneficial effects on iPTH.

The Effects and Safety of High Dose Vitamin D3 in Hemodialysis Patients

Background: Different studies have shown that hemodialysis patients require higher doses of Vitamin D3 (VD3) than the general population to achieve satisfactory replenishment. This study aims to assess the safety of such practice and its benefits on some of the parameters of Chronic Kidney Disease- Mineral and Bone Disorder (CKD-MBD). Methods: A single-center clinical trial assessing the benefits of high dose VD3 in hemodialysis patients. The dose of VD3 (300,000 IU) was administered orally and monthly from April to December 2020 (9 months) at the dialysis unit. The data analyzed were blood levels of calcium, phosphorus, alkaline phosphatase, 25(OH)D, 1,25(OH)2D and intact parathyroid hormone (iPTH) done every three months. Results: We could recruit a cohort of 23 patients. Blood levels of 25(OH)D increased significantly in 82.6% of the patients to above 30 ng/ml. A similar effect was observed with 1, 25(OH)2D levels. iPTH levels decreased significantly when levels of 25(OH)D exceeded 30ng/ml at the end of the nine months. Vitamin D serum levels were typically measured immediately before the next monthly dose was administered. Blood levels of calcium, phosphorus, and alkaline phosphatase were stable during the study period. No events of hypercalcemia were reported, and no patient discontinued the monthly VD3 supplementation. Conclusion: Monthly administration of a high dose of VD3 over a long period of nine months in hemodialysis patients was found to be safe and beneficial in VD3 replenishment. It also allowed a significant decrease in iPTH levels. Further studies are warranted to identify the therapeutic target level of 25(OH)D in hemodialysis patients, allowing beneficial effects on iPTH. (AU)

Untargeted Metabolomic Plasma Profiling of Emirati Dialysis Patients with Diabetes versus Non-Diabetic: A Pilot Study.

Diabetic kidney disease (DKD) is a severe irreversible complication of diabetes mellitus that further disturbs glucose metabolism. Identifying metabolic changes in the blood may provide early insight into DKD pathogenesis. This study aims to determine blood biomarkers differentiating DKD from non-diabetic kidney disease in the Emirati population utilizing the LC-MS/MS platform. Blood samples were collected from hemodialysis subjects with and without diabetes to detect indicators of pathological changes using an untargeted metabolomics approach. Metabolic profiles were analyzed based on clinically confirmed diabetic status and current HbA1c values. Five differentially significant metabolites were identified based on the clinically confirmed diabetic status, including hydroxyprogesterone and 3,4-Dihydroxymandelic acid. Similarly, we identified seven metabolites with apparent differences between Dialysis Diabetic (DD) and Dialysis non-Diabetic (DND) groups, including isovalerylglycine based on HbA1c values. Likewise, the top three metabolic pathways, including Tyrosine metabolism, were identified following the clinically confirmed diabetic status. As a result, nine different metabolites were enriched in the identified metabolic pathways, such as 3,4-Dihydroxymandelic acid. As a result, eleven different metabolites were enriched, including Glycerol. This study provides an insight into blood metabolic changes related to DKD that may lead to more effective management strategies.

Favorable Outcome of COVID-19 Pneumonia in a Kidney Transplant Recipient Treated with Tocilizumab.

The presentation of COVID-19 pneumonia in kidney transplant recipients is similar to that of the general population. However, in the former, it may have a worse clinical course. We report a kidney transplant patient affected by COVID-19 pneumonia whose condition worsened 9 days after the initial presentation. As no therapeutic guidelines on the subject are currently available, here we share our approach in the management of the immunosuppressive medications and the antiviral therapy and compare them to the scarce available data. We also expose the use of tocilizumab in our patient with excellent results.

Blood Neutrophil-to-Lymphocyte Ratio and Urine IL-8 Levels Predict the Type of Bacterial Urinary Tract Infection in Type 2 Diabetes Mellitus Patients.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the most common uropathogens causing UTI (urinary tract infection) in type 2 diabetes mellitus (T2DM). Circulatory inflammatory markers such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) are usually dysregulated during UTI. However, the differential regulation of these inflammatory signatures during E. coli and K. pneumoniae UTI in T2DM has not been determined. METHODS: A case-control study on 466 patients was performed to investigate the inflammatory signatures indicative of ESBL-E. coli and K. pneumoniae UTIs in T2DM. Serum CRP levels and blood NLR for these patients were determined and associated with E. coli and K. pneumoniae ESBL uropathogen using multivariate logistic regression analysis. Urinary interleukin 8 (IL-8) levels were also assessed and associated with these two UTI uropathogens in T2DM. The association of the two ESBL-uropathogens with the survival outcomes of T2DM patients was also analyzed using Cox-proportional hazard model. RESULTS: T2DM patients with ESBL-E. coli UTI had lower serum CRP levels (median, CRP mg/dL 33.7 vs 39.8, respectively; P=0.023) and higher blood NLR (median, NLR 3.2 vs 2.6, respectively; P=0.010) compared to those with K. pneumoniae UTIs (P<0.001). Moreover, in T2DM, the urinary IL-8 levels was higher in ESBL-E. coli compared to those with K. pneumoniae UTIs (P<0.0001). After adjusting for confounders, including age, gender, serum albumin, hemoglobulin, leukocytes, and platelet counts, T2DM patients with blood NLR ≥ 3.5 were at higher risk for ESBL-E. coli UTIs than ESBL-K. pneumoniae UTIs (odds ratio [OR], 3.61, 95% confidence interval, Cl, 1.49-8.73; P=0.004). Moreover, T2DM patients with ESBL-E. coli UTIs had higher all-cause mortality (hazard ratio [HR], 4.09; 95%, 1.14-14.59) than those with K. pneumoniae UTIs. CONCLUSION: Serum CRP levels, blood NLR, and IL-8 urinary levels differentiate ESBL-E. coli from K. pneumoniae UTIs in T2DM.

Association between Hepatitis C Virus Viremia and the rs12979860, rs2228145 and rs1800795 SNP (CT/AC/GG) Genotype in Saudi Kidney Transplant Recipients.

BACKGROUND: Hepatitis C virus (HCV) is a major health problem, particularly in high-risk groups such as kidney transplant recipients, where it can adversely affect graft survival and increase the relative risk for mortality. Recently, the role of genetic variation among HCV patients in determining the outcome of infections has been under investigation. OBJECTIVE: To investigate the association of single-nucleotide polymorphisms (SNPs) rs12979860 (located within the interleukin-28B locus), rs2228145 (interleukin-6 receptor) and rs1800795 (interleukin-6 promoter) with HCV viremia in renal transplant patients. MATERIALS AND METHODS: In this analytical cross-sectional study, 149 kidney transplant recipients, 82 males (median age: 41 years) and 67 females (median age: 45 years), were screened for HCV RNA in blood using real-time polymerase chain reaction and genotyped by sequencing (rs12979860) and restriction fragment length polymorphism (rs2228145 and rs1800795). RESULTS: HCV RNA was detected in 17 (11.41%) of the 149 patients. There was no statistically significant association between the studied SNPs and HCV viremia. However, a combination of the CT/AC/GG genotype was significantly associated with HCV viremia (odds ratio: 5.4). The genotype AA of rs2228145 in the IL-6 receptor was associated with viremia levels of >105 copies/ml (odds ratio: 5.96). CONCLUSION: To the best of the authors' knowledge, this is the first study that has shown that the CT/AC/GG genotype has an impact on HCV viremia in kidney transplant patients. Therefore, such SNP genotypes may potentially be used to identify transplant patients at risk of HCV infection.

Acute Focal Bacterial Nephritis: Two Cases and Review of the Literature.

RATIONALE: Acute focal bacterial nephritis (AFBN) has mainly been reported in pediatrics. It may be an underdiagnosed condition in adults because it resembles acute pyelonephritis (APN) in its clinical presentation. PRESENTING CONCERNS OF THE PATIENTS: Two young women (25 and 27 years old, respectively) presented with complaints compatible with a diagnosis of APN. However in both, fever was of high grade, persistent for several days in spite of antibiotic administration, and there was demonstrated worsening of the inflammatory biomarkers. A contrast-enhanced computed tomography (CECT) led to the diagnosis in both cases. DIAGNOSES: Contrast-enhanced computed tomography reveals the most sensitive and specific images of AFBN. This includes wedge-shaped lesions with decreased enhancement, which may be focal or multifocal. INTERVENTIONS INCLUDING PREVENTION AND LIFESTYLE: Antibiotic therapy for at least 3 weeks. OUTCOMES: Resolution of AFBN was obtained after 3 weeks of antibiotics. LESSONS LEARNED: Our 2 cases illustrate the importance of CECT imaging to confirm the diagnosis of AFBN. Interstitial bacterial inflammation may have a worse prognosis if not diagnosed early and efficiently treated. Unlike APN, the management of AFBN requires at least 3 weeks of antibiotics to prevent the development of renal scarring and renal abscess.

JUSTIFICATION: La pyélonéphrite aigüe focale (PNAF) a principalement été observée en pédiatrie. Il pourrait s'agir d'une affection sous-diagnostiquée chez les adultes puisque sa présentation clinique est similaire à la pyélonéphrite aigüe (PNA). PRÉSENTATION DES CAS: Nous présentons les cas de deux jeunes femmes (âgées respectivement de 25 et de 27 ans) qui présentaient des troubles compatibles avec une PNA. Cependant, dans les deux cas, la fièvre était élevée et a persisté plusieurs jours malgré l'administration d'antibiotiques. On a également observé une augmentation des biomarqueurs de l'inflammation. Un examen par CECT a mené au diagnostic de PNAF dans les deux cas. DIAGNOSTIC: La tomodensitométrie avec injection de contraste (CECT) révèle les images les plus sensibles et les plus spécifiques à la PNAF. Notamment les lésions cunéiformes avec intensification réduite pouvant être focale ou multifocale. INTERVENTIONS PRÉVENTION ET HABITUDES DE VIE: Un traitement antibiotique d'une durée de trois semaines. RÉSULTATS: La PNAF s'est résorbée après un traitement aux antibiotiques de trois semaines. ENSEIGNEMENTS TIRÉS: Nos deux cas illustrent l'importance de recourir à l'imagerie par CECT pour confirmer le diagnostic de la PNAF. Le pronostic de l'infection bactérienne interstitielle est susceptible de s'assombrir si celle-ci n'est pas diagnostiquée rapidement et traitée efficacement. Contrairement à la PNA, la prise en charge de la PNAF exige un traitement antibiotique d'au moins trois semaines afin de prévenir la fibrose rénale et la formation d'abcès rénaux.

Rhabdomyolysis and acute renal failure following prolonged surgery in the lithotomy position.

Operative positions commonly used in urogenital surgeries when perineal exposure is required include the lithotomy and the exaggerated lithotomy positions (LPs), which expose patients to the risk of rhabdomyolysis. We report a patient with bladder outflow obstruction, benign prostatic hypertrophy and a very large bladder stone, which was removed with cystoscopy and cystolitholapaxy in the LP. The procedure was complicated by posterior bladder perforation and abdominal distention leading to prolonged surgery duration (5.5 h). The patient developed rhabdomyolysis and acute renal failure (ARF) without compartmental syndrome. On the other hand, there was a potential role of glycine solution, used for bladder irrigation, in the appearance of ARF. Overall, our case shows that rhabdomyolysis and ARF can develop in operative positions, and duration of surgery is the most important risk factor for such complications.

Increased seroprevalence of human herpes virus-8 in renal transplant recipients in Saudi Arabia.

BACKGROUND: Human herpes virus-8 (HHV-8) is a herpes virus that is always associated with Kaposi's sarcoma. Previous studies suggested a high rate of Kaposi's sarcoma in renal transplant patients in Saudi Arabia. The aim of this study was to investigate the prevalence of HHV-8 in Saudi renal transplant recipients and healthy controls. METHODS: An immunofluorescence technique was used to detect antibodies to the latent nuclear antigen (LANA) of HHV-8 in renal transplant patients, members of a family affected with Kaposi sarcoma, as well as healthy controls. RESULTS: A significantly higher HHV-8 seroprevalence was detected in renal transplant recipients from Saudi Arabia (27 out of 150; 18%) and in members of a family affected with Kaposi sarcoma (seven out of 10; 70%) relative to the seroprevalence in healthy controls (10 out of 577; 1.7%). Seropositivity for HHV-8 in these transplant patients was not significantly influenced by: the existence of relatives with kidney failure, the donors' country of origin, the recipients' home region within Saudi Arabia, the haemodialysis centre, the time that elapsed since the renal transplantation operation and the immunosuppressive regimen used. CONCLUSION: The present results provide some explanation for the previously noted high incidence of Kaposi's sarcoma in Saudi transplant patients.