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Hanny Sawaf,1 Tariku T Gudura,1 Sylvester Dorobisz,1 Dianne Sandy,2 Xiangling Wang,1 Shane A Bobart2 1Department of Kidney Medicine, Cleveland Clinic, Cleveland, OH, USA; 2Department of Kidney Medicine, Cleveland Clinic Florida, Weston, FL, USACorrespondence: Shane A Bobart, Department of Kidney Medicine, 2950 Cleveland Clinic Blvd, Weston, FL, 33331, USA, Email bobarts@ccf.orgAbstract: Chronic kidney disease (CKD) is associated with significant morbidity and mortality worldwide. In recent years, our understanding of genetic causes of CKD has expanded significantly with several renal conditions having been identified. This review discusses the current landscape of genetic kidney disease and their potential treatment options. This review will focus on cystic kidney disease, glomerular disease with genetic associations, congenital anomalies of kidneys and urinary tract (CAKUT), autosomal dominant-tubulointerstitial kidney disease (ADTKD), inherited nephrolithiasis and nephrocalcinosis.Keywords: genetics, chronic kidney disease, end stage kidney disease, cystic kidney disease

Rationale & Objectives: Diabetic kidney disease (DKD) is a significant complication of diabetes mellitus, often leading to kidney failure. The absence of well-defined factors prevents distinguishing DKD from non-diabetic kidney disease (non-DKD; alternative primary diagnosis identified on kidney biopsy)., Study Design: Retrospective cohort study., Setting & Participants: This study assessed 1,242 patients with a history of diabetes from the Cleveland Clinic Kidney Biopsy Epidemiology Project between January 2015 and September 2021., Exposure: Proteinuria, retinopathy, A1c levels, and estimated glomerular filtration rate., Outcomes: Non-DKD, defined as an alternative primary diagnosis identified on kidney biopsy other than DKD., Analytical Approach: Multivariate logistic regression model with backward elimination method., Results: At the time of biopsy, the median (IQR) age was 63 (53-71 years) years, and 58.8% were men. The median hemoglobin A1c value was 6.7% (6.0%-8.1%), and the median serum creatinine level was 2.5 (1.6-3.9 mg/dL) mg/dL. Among 1,242 patients, 462 (37.2%) had DKD alone, and 780 (62.8%) had non-DKD. Among those with non-DKD, the most common diagnoses were focal segmental glomerulosclerosis (24%), global glomerulosclerosis otherwise not specified (13%), acute tubular necrosis (9%), IgA nephropathy (8%), antineutrophil cytoplasmic antibody vasculitis (7%), and membranous nephropathy (5%). Factors associated with having non-DKD on biopsy were having no retinopathy (vs retinopathy) (adjusted odds ratio [aOR], 3.98; 95% CI, 2.69-5.90), lower A1c levels (<7% vs ≥7%) (aOR, 3.08; 95% CI, 2.16-4.39), higher estimated glomerular filtration rate (≥60 vs <60 mL/min/1.73 m 2 ) (aOR, 2.39; 95% CI 1.28-4.45), microalbuminuria (<300 vs macroalbuminuria ≥300 [mg/g]) (aOR; 2.94; 95% CI, 1.84-4.72), and lower protein-creatinine ratio on random urine sample (<3 vs ≥3 mg/mg) (aOR; 1.80; 95% CI, 1.24-2.61)., Limitations: Selection bias of clinically indicated biopsies, not protocol biopsies, which likely represent a ceiling (maximum) for non-DKD., Conclusions: Among patients with diabetes undergoing kidney biopsy, 63% have findings in addition to DKD on biopsy. We identified clinical parameters associated with non-DKD in the setting of diabetes. This provides valuable information for clinicians when kidney biopsy should be considered among patients with diabetes to capture all etiologies of proteinuria and kidney dysfunction., (© 2024 The Authors.)

Our case depicts a challenging diagnosis of catastrophic antiphospholipid syndrome in a young patient with a heterogenous presentation with extensive clinical course, a wide range of investigations, including multimodality imaging, and multidisciplinary expertise, to initiate prompt treatment addressing multiorgan thrombotic injury., Competing Interests: No conflicts of interest for all authors., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Diabetic kidney disease (DKD) is a complication of diabetes that can lead to kidney failure. Over the years, several drugs have been developed to combat this disease. In the early 90s, angiotensin blockade (ACEi and ARBs) was introduced, which revolutionized the treatment of DKD. In recent years, newer drugs such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, endothelin antagonists, and mineralocorticoid receptor antagonists (MRA) have shown great promise in reducing albuminuria and protecting the kidneys. These drugs are being used in combination with lifestyle modifications, patient education, and risk factor modification to effectively manage DKD. In this review, we will explore the latest pharmacological options, their efficacy, and their potential to revolutionize the management of this debilitating disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bilen, Almoushref, Alkwatli, Osman, Mehdi and Sawaf.)

Background: The kidney biopsy is the gold standard for diagnosing glomerular diseases. Large-scale, epidemiologic studies describing the prevalence of kidney diseases are lacking, especially in the United States. We aimed to determine the spectrum of biopsy-proven kidney disease across the Cleveland Clinic enterprise., Methods: We identified all patients with a native kidney biopsy performed or reviewed at the Cleveland Clinic from January 2015 to September 2021. Retrospective chart review was performed to obtain clinical and demographic characteristics. Results were stratified by age, sex, race, and location to determine epidemiologic trends., Results: Of >9600 patients, we excluded transplant and donor biopsies and unavailable records, and included 4128 patients with native kidney biopsy data. The median age was 60 years, with 46% female patients. Self-reported racial demographics included 73% White, 22% Black, 3% multiracial, and 2% Asian background, with 5% Hispanic. Common diagnoses were: FSGS ( n =633, 15%), diabetic kidney disease (DKD) ( n =602, 15%), IgA nephropathy ( n =319, 8%), lupus nephritis (LN) ( n =289, 7%), pauci-immune glomerulonephritis ( n =275, 7%), membranous nephropathy ( n =211, 5%), and amyloidosis ( n =110, 3%). There were 3322 patients in Ohio, with 361 patients in Florida. Using multivariate analysis, those aged >70 years were more likely to have FSGS, whereas those <45 years were more likely to have IgA nephropathy or LN. Males were more likely to have FSGS or IgAN, and less likely to have LN. Black patients were more likely to have FSGS, DKD, or LN. Hispanic patients were more likely to have DKD. Finally, patients in Florida were more likely to have LN. There was no change in the disease spectrum before and during the COVID-19 pandemic., Conclusion: Our study catalogs the spectrum of biopsy-proven kidney disease across the Cleveland Clinic enterprise. This lays the foundation for glomerular disease clinical trials, and highlights the need for a standardized national kidney biopsy registry to bolster glomerular and kidney disease research in the United States., Competing Interests: S. Bobart reports having honorarium from Travere Therapeutics and other interests or relationships as Faculty for the GlomCon fellowship. L. Herlitz reports having consultancy agreements with ChemoCentryx; and reports having an advisory or leadership role on the ASN Kidney360 editorial board. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

A new series of sixteen new 2-arylamino-5,7-disubstituted-N-aryl-pyrazolo[1,5-a]pyrimidine-3-carboxamide derivatives was designed and synthesized. The antitumor activities of the new compounds were initially screened through the developmental therapeutics program at NCI-USA 60 cell line panel. 2-((2,4-dimethoxyphenyl)amino)-5,7-diphenylpyrazolo[1,5-a]pyrimidine-3-carboxamide (7a) was identified as a potential hit with a mean percentage of growth inhibition of 48.5% over the 60-NCI cancer cell lines whereas the other fifteen compounds ranged from 0.5 to 10.72%. In MTT assay, compound 7a exhibited IC 50 of 6.28 ± 0.26 µM and 17.7 ± 0.92 µM against HCT-116 colorectal cancer and WI-38 human lung fibroblast normal cell lines, respectively. In cell cycle analysis, compound 7a arrested cell cycle at G2/M phase. It was able to inhibit CDK1 (Cyclin-Dependent Kinase 1)/Cyc B (Cyclin B) complex at IC 50 161.2 ± 2.7 nM. The apoptosis-inducing ability of compound 7a was assessed through apoptosis detection flow-cytometry and gene expression analysis of apoptosis markers and caspase cascade which revealed that compound 7a exerts pro-apoptotic effect and increased expression of p53, Bax, cytochrome c, caspases (-3,-8, and-9), and decreased expression of Bcl-2. This suggests that the pro-apoptotic effect is exerted through the intrinsic pathway. The molecular docking study revealed a unique binding mode at the ATP binding pocket of CDK1/Cyc B/Cks2 through its 2,4-dimethoxyphenyl-amino. These results suggest that compound 7a could be a promising hit as a targeted protein kinase inhibitor which exerts its antitumor effect through CDK1 inhibition and pro-apoptotic action., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD) in the United States. Risk factor modification, such as tight control of blood glucose, management of hypertension and hyperlipidemia, and the use of renin-angiotensin-aldosterone system (RAAS) blockade have been proven to help delay the progression of DKD. In recent years, new therapeutics including sodium-glucose transport protein 2 (SGLT2) inhibitors, endothelin antagonists, glucagon like peptide-1 (GLP-1) agonists, and mineralocorticoid receptor antagonists (MRA), have provided additional treatment options for patients with DKD. This review discusses the various treatment options available to treat patients with diabetic kidney disease.

Objective: Hepatocellular carcinoma (HCC) is considered the highest recorded malignancy in Egypt. The shortage of appropriate biomarkers for early detection often results in the late diagnosis of the HCC. Circular RNAs (CircRNAs) are presented as long stranded non-coding RNA that combine covalently to make a sealed circular form which make them very stable. CircRNAs are known to have interpretative role in cancer development and metastasis., Aim: To examine the dysregulation of two new CircRNAs obtained from Circbase database (hsa&#95;circ&#95;0064286 and hsa&#95;circ&#95;0000475) in the serum of HCC patients as predictable diagnostic biomarkers of HCC and their correlation with some liver biochemical parameters., Methods: Sixty clinically diagnosed HCC Egyptian patients and 25 healthy volunteers were enrolled in the study. Expression levels of the selected CircRNAs was evaluated in subjects' serum. Moreover, correlation with liver biochemical parameters, sensitivity, and specificity of studied CircRNAs were estimated., Results: Both circular RNAs were significantly down regulated in HCC patients, which was negatively correlated with ALP, ALT, AST, AFP, and bilirubin levels. Circ&#95;0064286 showed more sensitivity and specificity (88.3% and 96%, respectively)., Conclusion: As far as we know, this is the first study that shed light on the expression levels of both circRNAs in Egyptian HCC patients. They may serve as potential biomarkers for HCC diagnosis. Moreover, those circRNAs draw attention as therapeutic targets for HCC through targeting their sponge miRNAs.

Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Abraham is a consultant for Shire.

We assessed safety and efficacy of rituximab in a prospective study of 36 patients, age 2.6 to 18.3 years, with severe chronic immune thrombocytopenic purpura (ITP). The primary outcome of sustained platelets above 50 x 10(9)/L (50,000/mm3) during 4 consecutive weeks, starting in weeks 9 to 12, was achieved by 11 of 36 patients (31%, confidence interval [CI], 16% to 48%). Median response time was 1 week (range, 1 to 7 weeks). Attainment of the primary outcome was not associated with age, prior pharmacologic responses, prior splenectomy, ITP duration, screening platelet count, refractoriness, or IgM reduction. First-dose, infusion-related toxicity was common (47%) despite premedication. Significant drug-related toxicities included third-dose hypotension (n = 1) and serum sickness (n = 2). Peripheral B cells were depleted in all subjects. IgM decreased 3.4% per week, but IgG did not significantly decrease. Rituximab was well tolerated, with manageable infusion-related side effects, but 6% of subjects developed serum sickness. Rituximab is beneficial for some pediatric patients with severe, chronic ITP.

Fear of leakage has inhibited many surgeons from performing one-layer anastomosis with a continuous absorbable suture for the outer layer. Ninety-three one-layer colonic anastomoses were performed using polyglycolic acid sutures in 92 patients. Mortality was low (1.1%) and intra-abdominal septic complications occurred in only 4 patients (4.4%). Superficial wound infections occurred in a further 6 patients (6.5%). The mean postoperative hospital stay was 13.2 d with more than 79% being discharged in 15 d.