Diabetic neuropathy: Molecular approach a treatment opportunity.

Diabetic neuropathy (DN) encompasses a group of clinical or subclinical manifestations involving a dysfunction in the peripheral nervous system. The cause of the dysfunction is the development of microvascular complications related to diabetes, a disease that affects about 381 million people worldwide. Approximately 50% of patients currently diagnosed with diabetes are expected to manifest DN in the next 10 years. The diagnosis can be made clinically by establishing a good patient history and delving into the symptoms to rule out other etiologies. Treatment of DN focuses on glycemic control and the use of medications to reduce pain, including NSAIDs, antidepressants and antiepileptic drugs. The pathogenesis is of multifactorial origin, associated with various metabolic, vascular, inflammatory and neurodegenerative disorders. The three fundamental cellular alterations participating in the development of DN are chronic inflammation, endothelial dysfunction and oxidative stress. Since the combination of all three is capable of giving rise to nerve ischemia and direct axonal injury, these factors play a key role in the development of polyneuropathy. However, neuronal and microvascular changes do not occur in the same way in all patients with DN, some of whom have no detectable blood abnormalities.

Antibody-Mediated Rejection Treatment With Bortezomib in Renal Transplant Recipients: A Single-Center 24-Month Follow-up Case Report.

INTRODUCTION: Antibody-mediated rejection (AMR) is related to a poor prognosis in graft survival, with 27% to 40% of patients experiencing graft loss within the first year. The mechanism of damage in AMR is mediated by donor-specific antibodies (DSA). No standard treatment for AMR exists, and conventional management includes high doses of steroids, plasmapheresis, intravenous immunoglobulin, and either rituximab or bortezomib. Because of the high cost of these medications and the lack of prospective studies to evaluate their efficacy and safety, their routine use is limited. In the following study, we describe the use of bortezomib for the treatment of AMR in 5 renal transplant recipients with a 24-month follow-up and compare this case with the reviewed literature. MATERIAL AND METHODS: Five cases of AMR diagnosed by biopsy are reported, and these patients received bortezomib at a rate of 1.3 mg/m2 on days 1, 4, 8, and 11; plasmapheresis; and 1 patient received 30 g of intravenous immunoglobulin. RESULTS: All patients received his or her first transplant; 4 were from a cadaveric donor, and 1 patient received thymoglobulin at a standard dose. All patients had maintenance therapy based on cyclosporine, mycophenolate mofetil, and prednisone, with an average baseline creatinine level of 1.3 mg/dL. The average days until rejection event were 952 days. DISCUSSION AND CONCLUSION: AMR treatment with bortezomib was effective, showing stable renal function at 24 months. Patients had adequate tolerance for administration. So far, these results contrast with the literature reviewed, so additional studies and follow-up are required for a new evaluation.

Metabolic Syndrome, a Real Barrier for Living Kidney Donor Transplant.

INTRODUCTION: Renal transplantation is the optimal renal replacement therapy. In Mexico, most of the kidney transplants are from living donors. It is essential to identify conditions that increase the risk of developing chronic kidney disease (CKD) in donors, such as metabolic syndrome (MS). MATERIALS AND METHODS: In retrospect from January 2008 to December 2018, the donation protocols for renal transplantation of the Hospital Central Sur Alta Especialidad "Picacho" were reviewed, classifying all the cases of donors by nephrectomy or no nephrectomy and describing the demographic characteristics, prevalence of metabolic diseases, and cause of rejection of the protocol. RESULTS: A total of 178 donors were studied: 82 women (46%), 96 men (54%), mean age of 42 years, average body mass index (BMI) 27.9 kg/m2, glomerular filtration rate (GFR) by Chronic Kidney Disease Epidemiology Collaboration 99 mL/min, 59 patients with grade I and II obesity (BMI ≥ 30 kg/m2), and 1 patient with morbid obesity (BMI ≥ 40 kg/m2). A total of 39 patients (22%) underwent nephrectomy and 139 (78%) did not. The following characteristics and alterations were found: Of the 139 patients who did not undergo nephrectomy, 91 had metabolic disorders, 20 had low GFR, 21 had albuminuria, and 4 recipients received cadaveric transplants, 3 due to critical conditions of the recipient. The metabolic alterations in the rejected donors were as follows: MS 54 (59%), prediabetes 55 (39%), newly diagnosed hypertension 70 (76%), diabetes mellitus 20 (14%), obesity 47 (51.6%), dyslipidemia 76 (83%), hyperuricemia 17 (12%). DISCUSSION: The prevalence of MS in apparently healthy donors is similar to that of other studies in Mexico. Both MS and its components are independently associated with an increased risk of cardiovascular disease and CKD. It has been shown that these donors have a greater degree of glomerular and interstitial fibrosis; therefore, diagnosis, prevention, and timely treatment in this group are important.