UNASSIGNED: Prader-Willi syndrome (PWS) is a multisystem genetic disorder caused by chromosomal imprinting gene defects, with approximately 70% of cases resulting from paternal deletion of the chromosomal region 15. The main clinical features include severe infantile hypotonia, early-onset childhood obesity, hyperphagia, and underdeveloped external genitalia. As individuals with PWS age, they may exhibit irritability, social dysfunction, impaired gonadal development, and metabolic syndrome. Previous literature places the prevalence of type 2 diabetes mellitus (T2DM) in PWS at approximately 7-24%. Oxytocin is a neuropeptide secreted by the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus and regulates energy metabolism, which is involved in PWS. Due to age limitations, very few patients progress to diabetic nephropathy during childhood, and reports of typical diabetic nephropathy in PWS during childhood are extremely rare. Dulaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist which can be used in the treatment of T2DM.
UNASSIGNED: This article reports a case of a child with PWS complicated by stage III diabetic nephropathy, providing a retrospective analysis of the diagnosis and treatment process, as well as a review of domestic and international literature, to enhance understanding of this condition. And this article provides a treatment idea for PWS patients with diabetic nephropathy.
UNASSIGNED: It is very important to enhance understanding of PWS. And we offer new diagnostic and possible therapeutic approaches for pediatric patients with diabetic nephropathy.

Idiopathic nodular glomerulosclerosis (ING) is a rare condition characterized by poor renal prognosis. The pathophysiology remains incompletely understood. Histologically, it closely resembles diabetic nephropathy. The development of this disease seems to be influenced by factors such as metabolic syndrome, particularly hypertension and glucose intolerance, along with active smoking. We report a case of ING in an obese 71-year-old male patient who had a long history of untreated hypertension and smoking. The patient underwent conservative treatment involving the administration of an angiotensin-2 receptor antagonist and dapagliflozin, resulting in favorable disease progression. Additional therapeutic measures, such as discontinuation of smoking and efforts toward weight loss, are strongly advised. Furthermore, regular screening for diabetes in the follow-up is crucial, as it can play a pathophysiological role in the disease and may manifest at a later stage, as observed in our clinical case.

The quantitative systems pharmacology (QSP) approach is widely applied to address various essential questions in drug discovery and development, such as identification of the mechanism of action of a therapeutic agent, patient stratification, and the mechanistic understanding of the progression of disease. In this review article, we show the current landscape of the application of QSP modeling using a survey of QSP publications over 10 years from 2013 to 2022. We also present a use case for the risk assessment of hyperkalemia in patients with diabetic nephropathy treated with mineralocorticoid receptor antagonists (MRAs, renin-angiotensin-aldosterone system inhibitors), as a prospective simulation of late clinical development. A QSP model for generating virtual patients with diabetic nephropathy was used to quantitatively assess that the nonsteroidal MRAs, finerenone and apararenone, have a lower risk of hyperkalemia than the steroidal MRA, eplerenone. Prospective simulation studies using a QSP model are useful to prioritize pharmaceutical candidates in clinical development and validate mechanism-based pharmacological concepts related to the risk-benefit, before conducting large-scale clinical trials.

The coexistence of primary membranous nephropathy (PMN), immunoglobulin A nephropathy (IgAN), and diabetic nephropathy (DN) in the same patient has been a subject of clinical and pathological investigation, yielding inconclusive results. The limited availability of cases and resource materials has hindered a comprehensive understanding of this phenomenon. We present the case of a 70-year-old Saudi Arabian man diagnosed with type 2 diabetes mellitus and nephrotic syndrome. A kidney biopsy revealed the coexistence of PMN, IgAN, and DN. The patient presented with an unusual and rare combination of PMN, IgAN, and DN. To address his condition, the patient consented to rituximab therapy and planned follow-up with the kidney transplant team. However, before the first dose of rituximab could be administered, the patient experienced severe septic shock secondary to pneumonia, which tragically led to his demise. The simultaneous occurrence of PMN, IgAN, and DN represents a rare and scarcely documented condition. The purpose of this article is to report this exceptional case, emphasizing the significance of further research to deepen the understanding of the underlying pathology behind these concurrent renal disorders. This report aims to shed light on the complexities of managing such complex cases and advancing therapeutic approaches in the future.

Simultaneous pancreas-kidney transplantation is an effective treatment option for end-stage renal disease with diabetes mellitus. Successful simultaneous pancreas-kidney transplantation allows achieving euglycemia, stabilizing existing microvascular complications and slowing their progression, improving the patient\'s quality of life, lipid and calcium-phosphorus metabolism, reducing the risks of cardiovascular events. Therefore, in view of the patient\'s severe general condition due to prolonged intoxication, hyperglycemia and other complications of chronic kidney disease, the earliest possible surgical treatment with minimization of the patient\'s stay on dialysis therapy is crucial to improve the outcome of transplantation.
Сочетанная трансплантация почки и поджелудочной железы является эффективным методом лечения терминальной стадии почечной недостаточности при сахарном диабете. Успешная трансплантация позволяет достичь эугликемии, стабилизировать имеющиеся микрососудистые осложнения и замедлить их прогрессирование, улучшить качество жизни пациента, показатели липидного, кальций-фосфорного обмена, уменьшить риски сердечно-сосудистых событий. Поэтому из-за тяжелого общего состояния пациента вследствие длительной интоксикации, гипергликемии и других осложнений хронической болезни почек для улучшения исхода трансплантации крайне важным является максимально раннее проведение оперативного лечения с минимизацией периода пребывания пациента на диализной терапии.

A 62-year-old man with type 2 diabetes was admitted because of a decrease in estimated glomerular filtration rate from 72 to 17.5 mL/min/1.73 m2 in 10 years and development of widespread bullous skin lesions. His hemoglobin A1c level had been maintained at 6.0-7.0% for 10 years with a dipeptidyl peptidase (DPP)-4 inhibitor. Skin biopsy showed typical bullous pemphigoid, and kidney biopsy showed tubulointerstitial nephritis with eosinophilic infiltration and glomerular endothelial cell proliferation. After discontinuing the DPP-4 inhibitor, skin lesions improved, and renal decline slowed. This case indicates that DPP-4 inhibitors can cause not only skin lesions but also renal disease.

The number of patients with diabetic nephropathy is increasing worldwide and it is important to understand the underlying pathological mechanisms of the disease. In early stage diabetic nephropathy, the hyperglycemic environment leads to vascular endothelial cell damage, resulting in overexpression of vascular endothelial growth factor (VEGF) in podocytes and renal pathology of glomerular hypertrophy, glomerular basement membrane thickening, and mesangial hyperplasia. In diabetic nephropathy, renal thrombotic microangiopathy (TMA) develops and the nephropathy progressively worsens in some cases of severe glomerular podocyte damage. Further, receptor tyrosine kinase inhibitors (RTKIs) may suppress VEGF secretion via VEGF receptor-2 tyrosine kinase inhibition in podocytes, which results in renal TMA and rapid deterioration of diabetic nephropathy. Osimertinib, a third-generation irreversible epidermal growth factor receptor (EGFR)-TKI, is approved as a first-line treatment agent for metastatic or locally advanced EGFR mutation-positive non-small cell lung cancer. We encountered a case of a patient with diabetic nephropathy with lung adenocarcinoma treated with osimertinib, whose condition deteriorated from early nephropathy to end-stage renal disease in approximately 4 months. The patient had early diabetic nephropathy, but the use of a RTKI suppressed VEGF expression in podocytes, resulting in the induction of renal TMA and the development of rapidly progressive diabetic nephropathy.

The associations between air pollution and diabetes mortality of different subtypes and complications were largely unclear. We performed an individual-level, time-stratified case-crossover study among over 0.9 million diabetes deaths from all administrative regions of Chinese mainland during 2013-2019. Daily concentrations of fine particles (PM2.5), coarse particles (PM2.5-10), nitrogen dioxide (NO2) and ozone (O3) were obtained for each decedent using high-resolution prediction models. Conditional logistic regression models were utilized to analyze the data. Each interquartile range increment in PM2.5, PM2.5-10, NO2 and O3 concentrations on lag 0-2 d increased the risks of overall diabetes mortality by 2.81 %, 1.92 %, 3.96 % and 2.15 %, respectively. Type 2 diabetes had stronger associations with air pollution than type 1 diabetes. Air pollutants were associated with diabetic ketoacidosis and diabetic nephropathy, but not other complications. The exposure-response curves were approximately linear with a plateau at higher concentrations of PM2.5, PM2.5-10, and NO2, while the associations for O3 appear to be statistically significant beyond 60 μg/m3. This nationwide study reinforces the evidence of higher risks of acute diabetic events following short-term air pollution exposure. We identified differential effects of air pollutants on various subtypes and complications of diabetes, which require further mechanistic investigations.

Collagenofibrotic glomerulopathy (CG) is a poorly understood kidney disease characterized by extensive deposition of abnormal type III collagen within the glomeruli. We report the case of a 25-year-old man with known type I diabetes mellitus who presented to the emergency department with diaphoresis, nephrotic-range proteinuria, hypertension, and elevated creatinine. Renal biopsy revealed combined collagenofibrotic glomerulopathy and diabetic nephropathy. This case highlights the clinicopathological features of type III collagen glomerulopathy and its possible association with diabetic nephropathy.

Uncontrolled diabetes can lead to diabetic nephropathy (DN). The aim of the study was to investigate the relationship between different dietary micronutrient patterns and risk of DN in women. This was a case-control study. One hundred and five patients had DN (defined as urinary mg of albumin per gram of creatinine ≥30 mg/g) were chosen as the case and 105 women without DN were chosen as control. Dietary intakes were assessed by a semi-quantitative food frequency questionnaire. Principal component analysis with varimax rotation was used to derive the micronutrient patterns. Patterns were divided into two groups of lower and higher than median. Logistic regression was used to discern and find the odds ratio (ORs) of DN, and its 95% confidence interval (CI) based on the micronutrient patterns in crude and adjusted model. Three patterns which were included, (1) mineral patterns such as chromium, manganese, biotin, vitamin B6, phosphorus, magnesium, selenium, copper, zinc, potassium, and iron, (2) water-soluble vitamin patterns such as vitamin B5, B2, folate, B1, B3, B12, sodium and C, and (3) fat-soluble vitamin patterns such as calcium, vitamin K, beta carotene, alpha tocopherol, alpha carotene, vitamin E, and vitamin A, were extracted. An inverse relationship was found between risk of DN and following mineral patterns and fat-soluble vitamin patterns in adjusted model (ORs = 0.51 [95% CI 0.28-0.95], p = .03) and (ORs = 0.53 [95% CI 0.29-0.98], p = .04), respectively. No relationship was seen between water-soluble vitamin patterns and risk of DN in crude and adjusted model but the significance was decreased in adjusted model. The risk of DN was 47% decreased after high adherence of fat-soluble vitamin patterns. In addition, we saw a 49% decrease of risk of DN in high adherence group of mineral patterns. The findings confirm that renal-protective dietary patterns can reduce risk of DN.