Plasmatic Klotho and FGF23 Levels as Biomarkers of CKD-Associated Cardiac Disease in Type 2 Diabetic Patients.

BACKGROUND: Research over the past decade has focused on the role of Klotho as a cardio protective agent that prevents the effects of aging on the heart and reduces the burden of cardiovascular disease CVD. The role of the interaction between fibroblast growth factor 23-(FGF-23)/Klotho in Klotho-mediated actions is still under debate. The main objective was to ascertain the potential use of plasmatic Klotho and FGF23 as markers for CKD-associated cardiac disease and mortality. METHODS: This was a prospective analysis conducted in an outpatient diabetic nephropathy clinic, enrolling 107 diabetic patients with stage 2⁻3 CKD. Patients were divided into three groups according to their left ventricular mass index and relative wall thickness. RESULTS: Multinomial regression analysis demonstrated that low Klotho and higher FGF-23 levels were linked to a greater risk of concentric hypertrophy. In the generalized linear model (GLM), Klotho, FGF-23 and cardiac geometry groups were statistically significant as independent variables of cardiovascular hospitalization (p = 0.007). According to the Cox regression model, fatal cardiovascular events were associated with the following cardiac geometric classifications; eccentric hypertrophy (p = 0.050); concentric hypertrophy (p = 0.041), and serum phosphate ≥ 3.6 mg/dL (p = 0.025), FGF-23 ≥ 168 (p = 0.0149), α-klotho < 313 (p = 0.044). CONCLUSIONS: In our population, Klotho and FGF23 are associated with cardiovascular risk in the early stages of CKD.

Acute Kidney Injury After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in a Portuguese Population.

Background: Acute kidney injury (AKI) after cytoreductive surgery followed by the infusion of hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is associated with a higher rate of major complications, resulting in prolonged hospitalization and increased mortality. Our objective was to evaluate the incidence of AKI and further progression to chronic kidney disease (CKD) in patients submitted to this procedure and recognize the associated risk factors. Methods: This retrospective study collected demographic, tumor-related, intraoperative, and postoperative data from 182 patients who underwent CRS/HIPEC from January 2016 to December 2019. Renal impairment was defined according to Kidney Disease Improving Global Outcomes criteria for AKI. We conducted univariate and multiple logistic regression analyses to assess the association between variables of interest and AKI. Results: Twenty-three patients (12.6%) developed AKI. In the AKI group, the risk for developing CKD was six times higher (odds ratio (OR) 6.48, confidence interval (CI) 1.601 - 26.255). Multivariate regression identified higher risk of developing AKI in patients who underwent HIPEC with cisplatin (OR 12.21, CI 1.26 - 109.70, P = 0.025), in each additional day spent in the intensive care unit (ICU) (OR 2.42, CI 1.07 - 5.45, P = 0.033), and an association for each unit increase in estimated glomerular filtration rate (eGFR) before HIPEC (OR 0.96, CI 0.94 - 0.98, P = 0.037) and AKI development. Conclusion: Patients who are at higher risk of AKI after CRS/HIPEC include those who performed cisplatin HIPEC regimen, had poorer preoperative renal function and had longer ICU stays. Early institution of preventive measures and frequent monitoring should be considered to minimize AKI risk and its associated morbidity, such as CKD progression.

Tip Lesion Variant of Focal and Segmental Glomerulosclerosis in a COVID-19 Patient.

Acute kidney injury is a common complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several pathologic findings are continually being reported, showing a probably multifactorial etiology. The authors present a case of a patient diagnosed with a tip lesion variant of focal segmental glomerulosclerosis (FSGS) in the setting of COVID-19. A 43-year-old African American female with no known renal disease presented to the emergency department with a 6-day history of fatigue, headache, hypoageusia, myalgia, cough, nausea, and vomiting. Laboratory tests confirmed SARS-CoV-2 infection. During hospitalization, there was a progressive decline in kidney function and evidence of nephrotic-range proteinuria without nephrotic syndrome. Biopsy specimen showed a tip lesion variant of FSGS. Genetic test revealed a homozygous variant of uncertain clinical significance (c.397G>A [p.V133M]) in the epithelial membrane protein 2 (EMP2) gene. To our knowledge, this is the first case report of a tip lesion in a COVID-19 patient with no renal history. More studies are warranted to define susceptible groups and identify the detailed mechanisms of COVID-19-related kidney disease that would allow for specific management of this complication.

A Less Common Cause of Acute Hepatitis in Kidney Transplant Recipients: A Case Series.

BACKGROUND: Hepatitis E virus (HEV) is a cause of significant morbidity and mortality, representing an important global public health problem. Immunocompetent patients with acute hepatitis E can clear the infection spontaneously; however, in approximately two thirds of cases, immunosuppressed patients, such as kidney transplant (KT) recipients, fail to clear the HEV infection and develop chronic hepatitis. PATIENTS AND METHODS: We report 3 cases of HEV infection in KT patients. Two presented only with laboratory abnormalities and elevated liver enzymes, and 1 presented with symptomatic disease motivating hospital admission. None was able to clear the infection spontaneously, and they were all treated with ribavirin, accompanied with reduction of immunosuppressive drugs. Adverse effects of the treatment were reported in 2 patients, and in 1 case, a dose reduction was necessary. All patients responded to the treatment and have no current evidence of active disease. No alterations of basal kidney function during or related to the treatment were registered. DISCUSSION: HEV screening in KT patients presenting with abnormal liver function of undetermined cause is fundamental, as it might have poorer outcomes in this specific population. The treatment with ribavirin seems to be safe and effective, although we must always be alert to potential side effects, maintaining a close follow-up of these patients.

Acquired perforating dermatosis with associated complicated cellulitis and amputation in a hemodialysis patient.

INTRODUCTION: Cutaneous manifestations related to chronic kidney disease (CKD) are common and associated with high morbidity. Acquired perforating dermatosis (APD) occurs mostly in diabetic or CKD patients, namely those undergoing hemodialysis. CASE REPORT: A 58-year-old male with type 2 diabetes, with long-term insulin use, several microvascular and macrovascular complications, and on maintenance hemodialysis for 5 years presented with a 1-week history of painful, pruritic, umbilicated papules and some punctiform necrotic lesions on his left forearm, both hands, and both amputation stumps. There was no evidence of infection or vascular alterations, and the patient was not responsive to an initial course of topical corticosteroid. These lesions rapidly evolved to larger, coalescent necrotic injuries, with aggravated pain, intense left-hand skin peeling, and the appearance of similar lesions in the trunk, requiring hospital admission. Calciphylaxis and APD were suspected. Skin biopsy was performed and directed treatment initiated, including intradialytic sodium thiosulfate. Histology findings were compatible with APD and also excluded findings suggestive of vasculitis or calciphylaxis. Soon after, difficult-to-treat cellulitis of the left hand and forearm progressed to critical ischemia and amputation. Microbiology analysis revealed Serratia marcescens as the causative agent. DISCUSSION: To our knowledge, there are no previously described cases of APD-related cellulitis. Its treatment can be particularly challenging, as lesions can persist and relapse, and chronic scars can develop. S. marcescens behaves as an opportunistic and difficult-to-treat pathogen, complicating the prognosis. CONCLUSION: APD can be associated with cellulitis and all of its complications in patients with underlying severe vasculopathy. Awareness of this complication in APD with early referral and aggressive treatment might improve the outcomes and quality of life of such patients.

FGF23-klotho axis as predictive factors of fractures in type 2 diabetics with early chronic kidney disease.

BACKGROUND: The aim of our study was to evaluate the relevance of FGF23-klotho axis in the predisposition for bone fractures in type 2 diabetic patients with early chronic kidney disease. METHODS: In a prospective study we included 126 type 2 diabetic patients with CKD stages 2-3 (from 2010 to 2017). We used descriptive statistics, ANOVA and chi-square test. Our population was divided into two groups according to the occurrence of a bone fracture event or not, and the groups were compared considering several biological and laboratorial parameters. We employed a multiple regression model to identify risk factors for bone fracture events and hazard ratios (HR) were calculated using a backward stepwise likelihood ratio (LR) Cox regression. RESULTS: Patients with a fracture event displayed higher levels of FGF-23, Phosphorus, PTH, TNF-α, OxLDL, HOMA-IR, calcium × phosphorus product and ACR and lower levels of Osteocalcin, α-Klotho, 25(OH)D3 and eGFR compared with patients without a fracture event (p < 0.001). The number of patients with a fracture event was higher than expected within inclining CKD stages (χ2, p = 0.06). The occurrence of fracture and the levels of TNF- α, klotho, 25(OH)D3 and OxLDL were found to predict patient entry into RRT (p < 0.05). Age, osteocalcin, α-Klotho and FGF-23 independently influenced the occurrence of bone fracture (p < 0.05). CONCLUSIONS: α-Klotho and FGF-23 levels may have a good clinical use as biomarkers to predict the occurrence of fracture events.