Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication ...of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality.
Hepatitis C virus(HCV)infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies.Patients with HCV infection were found to have ...a higher risk of end-stage renal disease.HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation.Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis(MPGN),membranous nephropathy,focal segmental glomerulosclerosis,fibrillary glomerulonephritis,immunotactoid glomerulopathy,IgA nephropathy,renal thrombotic microangiopathy,vasculitic renal involvement and interstitial nephritis.The most common type of HCV associated glomerulopathy is typeⅠMPGN associated with typeⅡmixed cryoglobulinemia.Clinically,typical renal manifestations in HCV-infected patients include proteinuria,microscopic hematuria,hypertension,acute nephritis and nephrotic syndrome.Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease:(1)antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes;(2)B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins;and(3)nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis.In patients with moderate proteinuria and stable renal functions,anti-HCV therapy is advised to be started as pegylated interferon-αplus ribavirin.However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations,immunosuppressive therapy with cyclophosphamide,rituximab,steroid pulses and plasmapheresis should be administrated.
Endothelial progenitor cells (EPC) are bone marrow derived or tissue-resident cells that play major roles in the maintenance of vascular integrity and repair of endothelial damage. Although EPCs may ...be capable of directly engrafting and regenerating the endothelium, the most important effects of EPCs seem to be depended on paracrine effects. In recent studies, specific microvesicles and mRNAs have been found to mediate the pro-angiogenic and regenerative effects of EPCs on endothelium. EPC counts have important prognostic implications in cardiovascular diseases (CVD). Uremia and inflammation are associated with lower EPC counts which probably contribute to increased CVD risks in patients with chronic kidney disease. Beneficial effects of the EPC therapies have been shown in studies performed on different models of CVD and kidney diseases such as acute and chronic kidney diseases and glomerulonephritis. However, lack of a clear definition and specific marker of EPCs is the most important problem causing difficulties in interpretation of the results of the studies investigating EPCs.
Contrast-induced acute kidney injury(CI-AKI) is oneof the most common causes of AKI in clinical practice.CI-AKI has been found to be strongly associated with morbidity and mortality of the ...patients.Furthermore,CI-AKI may not be always reversible and it may be associated with the development of chronic kidney disease.Pathophysiology of CI-AKI is not exactly understood and there is no consensus on the preventive strategies.CI-AKI is an active research area thus clinicians should be updated periodically about this topic.In this review,we aimed to discuss the indications of contrastenhanced imaging,types of contrast media and their impact on nephrotoxicity,major pathophysiological mechanisms,risk factors and preventive strategies of CI-AKI and alternative non-contrast-enhanced imaging methods.
Purpose
An outbreak of a novel respiratory disease due to coronavirus species was emerged in 2019 and named as Coronavirus Disease-2019 (COVID-19). Clinical and immunological factors affecting the ...course of COVID-19 in kidney transplant recipients (KTR) are not well-known.
Methods
In this prospective observational study, we presented 20 KTR with COVID-19 pnemonia and examined the factors predicting the severity of COVID-19. A total of 10 KTR without COVID-19 was used as control group. Lymphocyte subsets were determined by flow cytometry. In 13/20 patients, immunophenotyping was repeated 1 week later.
Results
Mean age of the patients was 50 ± 9 years. Patients were classified as mild–moderate (oxygen saturation: SO
2
> 90%) and severe disease groups (SO
2
≤ 90%). Serum albumin and hemoglobin were lower and CRP, fibrinogen and peak
d
-dimer were higher in severe group. Peak CRP was inversely associated with nadir SO
2
(
r
= − 0.68,
p
= 0.001). Neutrophil/lymphocyte ratio was higher in severe group (
p
= 0.01). CD3 + and CD4 + cells were lower and NK cell percentage (CD16 + 56 +) was higher in severe group. Percentage of spontaneously activated CD8 cells (CD8 + CD69 +) was higher in severe group. In comparison of KTR with and without COVID-19, CD8 + cells were lower but NK cell percentage was higher in KTR with COVID-19.
Conclusion
In this pilot study, increased NK cells, activated CD8 + cells and decreased CD3 + and CD4 + cells were associated with severity of COVID-19 in KTR. Peripheral immunophenotyping of lymphocyte subtypes may provide prognostic information about the clinical course of COVID-19 in KTR.
We aimed to present the demographic characteristics, clinical presentation, and outcomes of our multicenter cohort of adult KTx recipients with COVID-19.
We conducted a multicenter, retrospective ...study using data of patients hospitalized for COVID-19 collected from 34 centers in Turkey. Demographic characteristics, clinical findings, laboratory parameters (hemogram, CRP, AST, ALT, LDH, and ferritin) at admission and follow-up, and treatment strategies were reviewed. Predictors of poor clinical outcomes were analyzed. The primary outcomes were in-hospital mortality and the need for ICU admission. The secondary outcome was composite in-hospital mortality and/or ICU admission.
One hundred nine patients (male/female: 63/46, mean age: 48.4 ± 12.4 years) were included in the study. Acute kidney injury (AKI) developed in 46 (42.2%) patients, and 4 (3.7%) of the patients required renal replacement therapy (RRT). A total of 22 (20.2%) patients were admitted in the ICU, and 19 (17.4%) patients required invasive mechanical ventilation. 14 (12.8%) of the patients died. Patients who were admitted in the ICU were significantly older (age over 60 years) (38.1% vs 14.9%, p = 0.016). 23 (21.1%) patients reached to composite outcome and these patients were significantly older (age over 60 years) (39.1% vs. 13.9%; p = 0.004), and had lower serum albumin (3.4 g/dl 2.9-3.8 vs. 3.8 g/dl 3.5-4.1, p = 0.002), higher serum ferritin (679 μg/L 184-2260 vs. 331 μg/L 128-839, p = 0.048), and lower lymphocyte counts (700/μl 460-950 vs. 860 /μl 545-1385, p = 0.018). Multivariable analysis identified presence of ischemic heart disease and initial serum creatinine levels as independent risk factors for mortality, whereas age over 60 years and initial serum creatinine levels were independently associated with ICU admission. On analysis for predicting secondary outcome, age above 60 and initial lymphocyte count were found to be independent variables in multivariable analysis.
Over the age of 60, ischemic heart disease, lymphopenia, poor graft function were independent risk factors for severe COVID-19 in this patient group. Whereas presence of ischemic heart disease and poor graft function were independently associated with mortality.
Cholesterol-embolization syndrome (CES) is a multisystemic disease with various clinical manifestations. CES is caused by embolization of cholesterol crystals (CCs) from atherosclerotic plaques ...located in the major arteries, and is induced mostly iatrogenically by interventional and surgical procedures; however, it may also occur spontaneously. Embolized CCs lead to both ischemic and inflammatory damage to the target organ. Therefore, anti-inflammatory agents, such as corticosteroids and cyclophosphamide, have been investigated as treatment for CES in several studies, with conflicting results. Recent research has revealed that CES is actually a kind of autoinflammatory disease in which inflammasome pathways, such as NLRP3 and IL1, are induced by CCs. These recent findings may have clinical implications such that colchicine and IL1 inhibitors, namely canakinumab, may be beneficial in the early stages of CES.
Vascular calcification is associated with increased cardiovascular mortality in chronic hemodialysis patients. This prospective study investigated the relationship between serum osteoprotegerin, ...receptor activator of NF-κB ligand, inflammatory markers, and progression of coronary artery calcification score.
Seventy-eight hemodialysis patients were enrolled. Serum IL-1β, IL-6, TNF-α, osteoprotegerin, receptor activator of NF-κB, fetuin A, and bone alkaline phosphatase were measured by ELISA. Coronary artery calcification score was measured two times with 1-year intervals, and patients were classified as progressive or nonprogressive.
Baseline and first-year serum osteoprotegerin levels were significantly higher in the progressive than nonprogressive group (17.39±9.67 versus 12.90±6.59 pmol/L, P=0.02; 35.17±18.35 versus 24±11.65 pmol/L, P=0.002, respectively). The ratio of serum osteoprotegerin to receptor activator of NF-κB ligand at 1 year was significantly higher in the progressive group (0.26 0.15-0.46 versus 0.18 0.12-0.28, P=0.004). Serum osteoprotegerin levels were significantly correlated with coronary artery calcification score at both baseline (r=0.36, P=0.001) and 1 year (r=0.36, P=0.001). Importantly, progression in coronary artery calcification score significantly correlated with change in serum osteoprotegerin levels (r=0.39, P=0.001). In addition, serum receptor activator of NF-κB ligand levels were significantly inversely correlated with coronary artery calcification scores at both baseline (r=-0.29, P=0.01) and 1 year (r=-0.29, P=0.001). In linear regression analysis for predicting coronary artery calcification score progression, only baseline coronary artery calcification score and change in osteoprotegerin were retained as significant factors in the model.
Baseline coronary artery calcification score and serum osteoprotegerin levels were significantly associated with progression of coronary artery calcification score in hemodialysis patients.
Background
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. The course and progression of the disease is highly variable. In this study, we aimed to ...investigate the impact of clinical characteristics and basic biochemical parameters on progression of chronic kidney disease (CKD) in ADPKD patients.
Materials and methods
A total of 323 consecutive patients with ADPKD were enrolled into the study and followed with a mean duration of 100 ± 38 months. Patients were grouped as rapid progressors (RP) and slow progressors (SP) according to median rates of decline in glomerular filtration rate (ΔGFR) per year, namely 1 ml/min/year.
Results
History of macroscopic hematuria, urinary stone and smoking were more common in male patients; hepatic and other organ cysts were more common in female patients. ∆GFR/year was similar between males and females 0.95 (0–3.02) vs. 1.11 (0.10–2.74) ml/min/year,
p
= 0.21. History of smoking and pack-year of cigarettes smoked were significantly higher in the RP compared to the SP group (36 vs. 18 %,
p
= 0.01 and 5.24 ± 1.20 vs. 3 ± 1.32 pack-year,
p
= 0.02, respectively). Baseline 24 h-proteinuria was found to be significantly correlated with the percent decline of GFR (∆%GFR) per year (
r
= 0.303, 0.001). In Cox regression analysis for predicting the progression of CKD, age, hypertension, urinary stone and proteinuria were retained as the significant independent factors predicting progression of CKD in the model.
Conclusion
Baseline proteinuria was significantly correlated with ∆%GFR per year. Hypertension and proteinuria were found to be the major treatable risk factors for the progression of CKD in ADPKD patients.
Cholesterol-embolization syndrome (CES) is a multisystemic disease with various clinical manifestations. CES is caused by embolization of cholesterol crystals (CCs) from atherosclerotic plaques ...located in the major arteries, and is induced mostly iatrogenically by interventional and surgical procedures; however, it may also occur spontaneously. Embolized CCs lead to both ischemic and inflammatory damage to the target organ. Therefore, anti-inflammatory agents, such as corticosteroids and cyclophosphamide, have been investigated as treatment for CES in several studies, with conflicting results. Recent research has revealed that CES is actually a kind of autoinflammatory disease in which inflammasome pathways, such as NLRP3 and IL1, are induced by CCs. These recent findings may have clinical implications such that colchicine and IL1 inhibitors, namely canakinumab, may be beneficial in the early stages of CES. Keywords: cholesterol crystals, atherosclerosis, inflammation, autoinflammation, corticosteroids, interleukin 1, NLRP3, colchicine, canakinumab
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