Polycystic kidney disease (PKD) is a group of inherited disorders characterized by cystic lesions in the kidneys and multiple organs, primarily including autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). ADPKD is mainly caused by variations in the PKD1 and PKD2 genes. Its clinical manifestations include progressive renal cyst growth, hypertension, and multi-system complications. ARPKD, on the other hand, is primarily caused by mutations in the PKHD1 gene. It commonly occurs in infants and young children, with hepatorenal cystic fibrosis being a key feature. Although there is currently no cure for PKD, the integration of multi-omics and precision medicine strategies holds promise for optimizing patient management and improving outcomes in the future. This review summarizes the genetic basis, pathogenic mechanisms, diagnostic techniques, and therapeutic advances in PKD, providing a reference for clinical practice and research.
Humans ; Polycystic Kidney Diseases/genetics* ; TRPP Cation Channels/genetics* ; Mutation ; Polycystic Kidney, Autosomal Dominant/therapy* ; Receptors, Cell Surface

OBJECTIVES

In the past decade, the prevalence of diabetes in the Philippines has been increasing. The prevalence of diabetes is 7.1% and it is the sixth leading cause of death among adults. Preventive measures to address the incidence of diabetes, as well as diabetes-related complications, have been in place. However, knowledge of the risk factors for developing cardiovascular or renal-related Type 2 Diabetes Mellitus (T2DM) complications has numerous benefits for T2DM patients. This study aimed to describe common risk factors among Filipino T2D patients which increase their risk of developing cardiorenal complications including Heart Failure and CKD. Furthermore, the study aimed to assess the
awareness of T2DM patients regarding these risk factors

METHODS

A clinic-based cross-sectional survey among Filipinos with T2DM Philippines was conducted in the different regions in the Philippines from April 2021 to January 2022. The study participants were 16,268 patients of various ages and sex, however, only 11,578 of them answered the form completely. The patients and their corresponding physicians answered a validated self-assessment form on whether they had 8 identified risk factors for T2DM.

RESULTS

This survey identified Hypertension as the most common risk factor present in 96.49% of T2DM patients followed by Dyslipidemia (82.56%), Family History of CVD (77.11%), Obesity (59.66%), Kidney Disease (38.08%), Personal History of CVD (36.22%), Smoking (35.49%) and Family History of Kidney Disease (33.05%). Most patients were aware of the presence of these risk factors. However, there were some identified by the physician but unknown to the patient. In decreasing order of frequency, these were personal history of heart and blood vessel diseases (7.19%), followed by family history of kidney disease (5.44%) and smoking (5.1%).

CONCLUSION

This survey was able to identify crucial risk factors in developing T2DM complications that are most common among T2DM patients in the Philippines. Furthermore, for the first time, the study was able to show the level of awareness of T2DM patients regarding the risk factors that they have in developing these complications. These data show the importance of determining and addressing the common risk factors in preventing T2DM complications. Moreover, identification of these risk factors is an important step in prevention of cardiorenal complications.

Identification (psychology) ; Cross-sectional Studies ; Diabetes Mellitus, Type 2 ; Diabetes Complications ; Kidney Diseases

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multi-system disease that presents significant diagnostic challenges due to its complexity and low incidence (White and Dubey, 2023). It affects males and females equally, though males may exhibit more active disease at diagnosis and often require more aggressive treatment (Liu et al., 2023). The hallmark features of EGPA include delayed-onset asthma, eosinophilia in tissues and blood, and vasculitis affecting small to medium-sized arteries (White and Dubey, 2023). EGPA falls under the category of antineutrophil cytoplasmic antibody (ANCA)‍-associated vasculitis (AAV), whereas only about half of EGPA patients test positive for ANCA (Khoury et al., 2023).
Humans ; Male ; Hemorrhage/etiology* ; Granulomatosis with Polyangiitis/complications* ; Heart Arrest/etiology* ; Early Diagnosis ; Eosinophilia/diagnosis* ; Kidney Diseases/etiology* ; Churg-Strauss Syndrome/complications* ; Middle Aged

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with Type 2 Diabetes Mellitus (T2DM) and is associated with chronic kidney disease (CKD). The aim of this cross-sectional study was to determine the association of Fibrosis-4 (FIB-4) index with CKD among T2DM patients with concomitant NAFLD.

METHODOLOGY

A single center, analytical cross-sectional study was conducted among 216 T2DM patients with concomitant NAFLD. Clinical data were obtained via retrospective review of medical charts. The outcome of interest was CKD which was based on self-report obtained from medical charts or estimated Glomerular Filtration Rate (eGFR) < 60mL/min result nearest to the date of liver ultrasound. FIB-4 index of patient on admission was calculated using an online calculator and subjects were grouped into low, moderate and high risk of developing severe fibrosis depending on their FIB-4 index. In order to determine the association between FIB-4 index and CKD, logistic regression analysis was performed.

RESULTS

Higher FIB-4 index was found to be significantly associated with CKD. Patients with FIB-4 index of 1.45-3.25 (moderate risk) and > 3.25 (high risk) have about 3 times higher odds of CKD. However, after controlling for the significant confounders, only those who belong to high-risk group was found to be associated with CKD.

CONCLUSION

This study has demonstrated that FIB4 index > 3.25, an index of liver fibrosis, is significantly associated with development of CKD in T2DM patients with concomitant NAFLD.

Human ; Diabetes Mellitus ; Non-alcoholic Fatty Liver Disease ; Chronic Kidney Diseases ; Renal Insufficiency, Chronic

The most common cause of mortality after a kidney transplant is a cardiovascular event. This is why most patients with poor cardiovascular status are denied a transplant. A 70-year-old male, ESRD from hypertensive nephropathy, was declined renal transplantation in the United States for advanced age, severe coronary disease and abdominal aortic aneurysm. The patient sought a second chance at a possible transplantation here in the Philippines. After a comprehensive cardiovascular evaluation, he underwent coronary artery bypass graft for a three-vessel disease followed by endovascular aneurysm repair (EVAR) which he tolerated well. After four weeks, he underwent a living-related kidney transplantation with immediate allograft function. On postoperative day 5, after catheter removal, the patient was unable to void spontaneously. He was diagnosed with benign prostatic obstruction and underwent transurethral resection of the prostate. He tolerated this and voided freely since catheter removal. One year later, the patient has a functioning allograft and stable cardiac status. High risk patients with cardiovascular disease may be given a chance at kidney transplantation after a meticulous evaluation and optimization.

Human ; Male ; Aged: 65-79 Yrs Old ; Evar ; Allografts ; Aneurysm ; Aortic Aneurysm ; Aortic Aneurysm, Abdominal ; Arteries ; Cardiovascular Diseases ; Catheters ; Coronary Artery Bypass ; Disease ; Coronary Disease ; Endovascular Aneurysm Repair ; Evaluation Studies As Topic ; Kidney ; Kidney Failure, Chronic ; Kidney Transplantation ; Male ; Mortality ; Patients ; Philippines ; Prostate ; Risk ; Transplantation ; Transplants ; United States

BACKGROUND

Worldwide, kidney transplantation is done as a renal replacement therapy for end-stage kidney disease patients. Lymphocoele is a common complication following renal transplantation, with an incidence varying between 0.6% and 33.9%. The use of the electrothermal bipolar sealing device (LigaSure) has proven superior to other vessel sealing techniques in several reports. As such, LigaSure device is expected to provide an alternative method to the standard silk-tie method during kidney transplantation.

OBJECTIVES

To describe our experience on using Ligasure device in kidney transplantation at the National Kidney and Transplant Institute.

METHODS

A prospective descriptive cross sectional research design among patients who underwent iliac vessel dissection using Ligasure device during kidney transplantation. Clinical outcomes were determined including operative time during iliac vessel dissection using LigaSure device, total and average JP drain output. Incidence of lymphocoele was observed by performing an allograft ultrasound on post operative day 14, 60 and 90.

RESULTS

Ultrasonographically, none of the patients in this study developed a lymphocele. Average use of Ligasure device during iliac vessel dissection was 16.92 minutes. Average daily JP drain output was 123mL and average JP drain output prior to JP drain removal was 25.44mL.

CONCLUSION

We did not observe any incidence of lymphocoele among patients wherein Ligasure device was used during iliac vessel dissection. Routine use of Ligasure device can be done without the risk of lymphocoele formation and can serve as an alternative from the traditional silk-tie method during iliac vessel dissection.

Human ; Kidney ; Kidney Diseases ; Kidney Failure, Chronic ; Kidney Transplantation ; Renal Replacement Therapy

BACKGROUND: Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends. METHODS: Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson's correlation analysis was used to determine the association between ASR and sociodemographic index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040. RESULTS: Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively. CONCLUSION NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.
Humans ; Noncommunicable Diseases/epidemiology* ; Global Burden of Disease ; Disability-Adjusted Life Years ; Male ; Female ; Risk Factors ; Middle Aged ; Kidney Diseases/epidemiology* ; Bayes Theorem ; Adult ; Aged ; Global Health ; Quality-Adjusted Life Years

Cellular senescence, stable cell cycle arrest that can be triggered in normal cells in response to various intrinsic and extrinsic stressors, has been highlighted as one of the most important mechanisms involved in kidney diseases. It not only serves as a fundamental biological process promoting normal organogenesis and successful wound repair but also contributes to organ dysfunction, tissue fibrosis, and the generalized aging phenotype. Moreover, senescent cells exhibit reduced regenerative capacity, which impairs renal function recovery from injuries. Importantly, senescent cells are involved in immune regulation via secreting a diverse array of proinflammatory and profibrotic factors known as senescence-associated secretory phenotype (SASP) with autocrine, paracrine, and endocrine activities. Thus, eliminating detrimental senescent cells or inhibiting SASP production holds great promise for developing innovative therapeutic strategies for kidney diseases. In this review, we summarize the current knowledge of the intricate mechanisms and hallmarks of cellular senescence in kidney diseases and emphasize novel therapeutic targets, including epigenetic regulators, G protein-coupled receptors, and lysosome-related proteins. Particularly, we highlight the recently identified senotherapeutics, which provide new therapeutic strategies for treating kidney diseases.
Humans ; Cellular Senescence/genetics* ; Kidney Diseases/pathology* ; Senescence-Associated Secretory Phenotype/physiology* ; Animals ; Epigenesis, Genetic/physiology*

Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*

This study investigates the reproductive protective effect and potential mechanism of Cistanches Herba extract(CHE) on a rat model of kidney-Yang deficiency induced by adenine. Rats were randomly divided into five groups: normal, model, low-dose CHE(0.6 g·kg~(-1)·d~(-1)), high-dose CHE(1.2 g·kg~(-1)·d~(-1)), and L-carnitine(100 mg·kg~(-1)·d~(-1)). The rats were administered adenine(200 mg·kg~(-1)·d~(-1)) by gavage for the first 14 days to induce kidney-Yang deficiency, while simultaneously receiving drug treatment. After 14 days, the modeling was discontinued, but drug treatment continued to 49 days. The content of components in CHE was analyzed by high-performance liquid chromatography. The adenine-induced kidney-Yang deficiency model was assessed through symptom characterization and measurement of testosterone(T) levels using an enzyme-linked immunosorbent assay kit. Pathological damage to the testis and epididymis was evaluated based on the wet weight and performing hematoxylin-eosin staining. Sperm density and motility were measured using computer-aided sperm analysis, and sperm viability was assessed using live/dead sperm staining kits, and sperm morphology was evaluated using eosin staining, thereby determining rat sperm quality. Metabolomics was used to analyze changes in serum metabolites, enrich related metabolic pathways, and explore the mechanism of CHE in improving reproductive function damage in rats with kidney-Yang deficiency syndrome. Compared to the normal group, the model group exhibited significant kidney-Yang deficiency symptoms, reduced T levels, decreased testicular and epididymal wet weights, and significant pathological damage to the testis and epididymis. The sperm density, motility, and viability decreased, with an increased rate of sperm abnormalities. In contrast, rats treated with CHE showed marked improvements in kidney-Yang deficiency symptoms, restored T levels, alleviated pathological damage to the testis and epididymis, and improved various sperm parameters. Metabolomics results revealed 286 differential metabolites between the normal and model groups(191 upregulated and 95 downregulated). Seventy-five differential metabolites were identified between the model and low-dose CHE groups(21 upregulated and 54 downregulated). A total of 24 common differential metabolites were identified across the three groups, with 22 of these metabolites exhibiting opposite regulation trends between the two comparison groups. These metabolites were primarily involved in linoleic acid metabolism, ether lipid metabolism, and pantothenic acid and coenzyme A biosynthesis, as well as metabolites including 13-hydroperoxylinoleic acid, lysophosphatidylcholine, and pantethine. CHE can improve kidney-Yang deficiency symptoms in rats, alleviate reproductive organ damage, and enhance sperm quality. The regulation of lipid metabolism may be a potential mechanism through which CHE improves reproductive function in rats with kidney-Yang deficiency. The potential bioactive compounds of CHE include echinacoside, verbascoside, salidroside, betaine, and cistanoside A.
Animals ; Male ; Rats ; Yang Deficiency/physiopathology* ; Metabolomics ; Kidney/physiopathology* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Cistanche/chemistry* ; Kidney Diseases/metabolism* ; Testis/metabolism* ; Humans ; Reproduction/drug effects* ; Testosterone/blood*