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Background Drug-drug interactions are frequently observed in kidney transplant recipients due to polypharmacy and use of immunosuppressants. However, there is only one study evaluating clinically relevant potential drug-drug interactions of immunosuppressants specially in kidney transplant recipients by means of online databases and Stockleys Drug Interactions, as a gold standard. Aim This study aimed to compare four online databases used frequently to determined clinically relevant potential drug-drug interactions of immunosuppressants in kidney transplant recipients according to the Renal Drug Handbook. Method This was a descriptive cross-sectional study conducted between October 1, 2019, and March 18, 2020, in the nephrology ward of Ankara University School of the Medicine, Ibn-i Sina Hospital. In total, 52 adult patients' discharge prescriptions were retrieved from their medical records and analyzed retrospectively. Micromedex®, Lexicomp®, Medscape, and Drugs.com databases were used to evaluate drug interactions. The Renal Drug Handbook was used as a gold standard to do specificity and sensitivity analysis. Results A total of 127 potential drug-drug interactions between the immunosuppressants and co-medications were detected by at least one online database. 32 (25.2%) of these were approved as clinically relevant potential drug-drug interactions by the Renal Drug Handbook. Lexicomp® and Drugs.com have exhibited the highest sensitivity (0.72 and 0.75) while Micromedex® has shown the highest specifity (0.83). Furthermore, the highest positive predictive value has been observed in Micromedex® (0.53). Micromedex® and Medscape had the highest negative predictive value (0.83 and 0.82). However, the kappa value of all was low. The values of inter-rater agreement (Kappa index) between online databases and the Renal Drug Handbook were weak (range 0.05-0.36). In addition, only 11 (8.7%) of potential drug-drug interactions were identified by all online databases. Conclusion This study showed that there was a weak compatibility between each database examined and the Renal Drug Handbook to detect clinically relevant potential drug-drug interactions for immunosuppressants in kidney transplant recipients. Therefore, we suggest that although databases might be practical to take a quick glance in detection of potential drug-drug interactions between immunosuppressants and co-medications, the data should be evaluated in detail and interpreted with caution in combination with a reference book like Renal Drug Handbook., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Cytomegalovirus infection is an important complication in immunocompromised patients. As few studies have shown that cyclophosphamide treatment is a risk factor for cytomegalovirus infection in patients with glomerulonephritis, we aimed to describe the frequency and risk factors of cytomegalovirus infection in glomerulonephritis patients treated with cyclophosphamide., Methods: We prospectively recruited 43 cytomegalovirus seropositive patients with glomerulonephritis treated with cyclophosphamide. We screened all patients for viral DNA monthly during treatment. Patients were compared for age, sex, glomerular pathology, renal function and clinical status regarding development of cytomegalovirus infection before and after the treatment., Results: Cytomegalovirus infection was detected in 10 (23.3%) patients, most commonly within the first 2 months of cyclophosphamide treatment. All patients recovered without any cytomegalovirus-related complications. Patients with cytomegalovirus infection had higher serum creatinine (4.2 ± 3.2 vs. 1.9 ± 1.8 mg/dl, p = 0.006) and lower estimated glomerular filtration rate (29 ± 11 vs. 65 ± 8 ml/min/1.73 m 2 , p = 0.016) at diagnosis compared with cytomegalovirus infection non-occurred patients. In addition, number of patients presented with rapidly progressive glomerulonephritis were higher in cytomegalovirus infection group (80.0% vs. 27.3%, p = 0.007). Moreover, cytomegalovirus infection was associated with prolonged hospital stay (54 ± 7 vs. 29 ± 6 days, p = 0.027)., Conclusion: Cytomegalovirus infection is a common complication in glomerulonephritis patients treated with cyclophosphamide in this prospective study. Routine monitoring and prophylaxis should be considered for these high-risk patients., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Aims: Arterial stiffness is a risk factor for chronic kidney disease progression (CKD). Pulse pressure is a surrogate marker of arterial stiffness. It is unclear if pulse pressure predicts CKD progression in type 2 diabetes mellitus., Methods: This was prospective study involving 1494 patients with estimated glomerular filtration rate (eGFR) ≥ 15 ml/min/1.73 m 2 . Carotid-femoral pulse wave velocity was measured using applanation tonometry. Pulse pressure was calculated as difference between systolic and diastolic blood pressures. CKD progression was defined as worsening of eGFR categories (stage 1, ≥ 90 ml/min/1.73 m 2 ; stage 2, 60-89 ml/min/1.73 m 2 ; stage 3a, 45-59 ml/min/1.73 m 2 ; stage 3b, 30-44 ml/min/1.73 m 2 ; stage 4; 15-29 ml/min/1.73 m 2 ; and stage 5, < 15 ml/min/1.73 m 2 ) with ≥ 25% decrease in eGFR from baseline., Results: After follow-up of up to 6 years, CKD progression occurred in 33.5% of subjects. Subjects in 2nd, 3rd and 4th quartiles of peripheral pulse pressure experienced higher risk of CKD progression with unadjusted hazard ratios (HRs) 1.55 [95% confidence interval (CI) 1.13-2.11; p = 0.006], 2.58 (1.93-3.45; p < 0.001) and 3.41 (2.58-4.52; p < 0.001). In the fully adjusted model, the association for 2nd, 3rd and 4th quartiles remained with HRs 1.40 (1.02-1.93; p = 0.038), 1.87 (1.37-2.56; p < 0.001) and 1.75 (1.25-2.44; p = 0.001) respectively. Similarly, 2nd, 3rd and 4th quartiles of aortic pulse pressure were associated with higher hazards of CKD progression with HRs 1.73 (1.25-2.40; p = 0.001), 1.65 (1.18-2.29; p = 0.003) and 1.81 (1.26-2.60; p = 0.001). Increasing urinary albumin-to-creatinine ratio accounted for 44.0% of the association between peripheral pulse pressure and CKD progression., Conclusions: Individuals with high pulse pressure were more susceptible to deterioration of renal function. Pulse pressure could potentially be incorporated in clinical practice as an inexpensive and readily available biomarker of renal decline in type 2 diabetes mellitus. Graphic abstract., (© 2021. Italian Society of Nephrology.)

Viral nephropathy is a term defines glomerular, tubular and/or vascular injury in kidney caused by viruses itself or virus-induced immune mechanisms. It is difficult to prove causality between the renal disease and the viral infection, however, renal biopsy findings can help in this regard. Several viruses such as hepatitis B and C, Human immun deficiciency virus (HIV), Hantavirus, Cytomegalovirus (CMV), an recently Coronavirus are shown to affect the kidney. Treatment of viral nephropathies are unique regarding the diagnosis which can be made only with renal biopsy in most of the situations. We present two patients presented with acute kidney injury and thrombocytopenia caused by different viruses (Hantavirus and HIV) that affect multiple areas in kidney that revealed with kidney biopsy. Supportive treatment in the patient with Hantavirus nephropathy and HIV treatment along with eculizumab and supportive treatment in the patient with HIVAN were successfully implemented.

Purpose: Cytomegalovirus (CMV) infection is an important complication in organ and bone marrow recipients as well as patients infected with HIV. Although screening and prophylaxis have been defined in these patients, there are few data about the frequency of CMV disease in glomerular diseases treated by immunosuppression., Methods: We recruited 133 patients with glomerular diseases treated by immunosuppression between 2006 and 2013. Patients who had any symptoms suggestive of CMV disease were screened for viral DNA. Immunosuppressive treatments were as follows: Group 1, steroid only; Group 2, steroid with cyclophosphamide (CP); Group 3, steroid with cyclosporine A; and Group 4, steroid with mycophenolate mofetil or azathioprine., Results: Patients developing CMV and non-CMV disease were compared for age, sex, renal pathology, hypertension, diabetes, baseline creatinine, and estimated glomerular filtration rate, and immunosuppressive regimen. At follow-up, 55 patients were tested for CMV disease during immunosuppressive treatment. Twenty-six patients had CMV DNA positivity of 1,112-205,500 copies/mL. Patients with CMV disease were all seen within the first 5 months of immunosuppressive treatment, and the disease was observed most commonly (14 patients, 53 %) in the first 2 months of treatment. Multiple regression analysis revealed that high baseline creatinine levels, older age, and use of steroids with CP were independent risk factors for development of CMV disease., Conclusions: CMV disease is not an uncommon complication in patients with glomerular diseases treated by immunosuppression. Further prospective studies and prophylaxis should be addressed in future studies, including particular groups of patients.

Background: Nitric oxide (NO), synthesized from LS: -arginine by the enzyme endothelial nitric oxide synthase (eNOS), is a potent vasodilator and has been implicated in mediating insulin-induced uptake and metabolism of glucose in skeletal muscle. Polymorphisms of the eNOS gene have been associated with altered eNOS activity and NO levels. Although several factors have been demonstrated for new onset diabetes mellitus after transplantation (NODAT), determining a genetic susceptibility for all patients requires further study. In our study, we evaluated the relationship between eNOS gene intron 4 polymorphism and NODAT in kidney allograft recipients., Methods: A total of 82 consecutive patients who received their first kidney transplantation and maintained graft function for at least a 12-month post-transplant period and who used triple therapy including cyclosporin A (CsA) for maintenance immunosuppression were included. PCR-RFLP was used for genetic analyses., Results: Nine of 82 patients (11%) developed NODAT. Concerning the prevalence of eNOS intron 4 gene polymorphism, a significantly higher percentage of 4a allele carriers developed NODAT than non-carriers [6/26 (23.1%) versus 3/56 (5.4%), P = 0.02]. Compared with non-diabetics, NODAT patients were older (P = 0.04), had higher rate of hepatitis C (P < 0.05) and higher body mass index at the time of transplantation (P = 0.03). In regression analyses, having a 4a allele of the eNOS gene intron 4 polymorphism (P = 0.02) and HCV seropositivity (P = 0.03) were found to be independent risk factors for the development of NODAT., Conclusions: These findings suggest that carrying a 4a allele of the eNOS gene intron 4 polymorphism is associated with NODAT. This may help us to further understand the individual risk for development of NODAT in kidney allograft recipients under CsA treatment.

Background: Both thrombomodulin (TM) and endothelial protein C receptor (EPCR) are candidate biomarkers of endothelial damage and have a role of anti-thrombotic defense mechanism in vascular structure. In this study, we aimed to investigate soluble EPCR (sEPCR), soluble TM (sTM) and tumor necrosis factor-alpha (TNF-alpha) levels in hemodialysis (HD) and renal transplant (RTx) recipients., Methods: Twenty-seven RTx recipients and 15 HD patients were recruited to the study. RTx recipients were evaluated before and 3 months after transplantation. Plasma sEPCR, sTM and TNF-alpha levels were measured at baseline and 3 months later in both groups. Moreover, 27 healthy subjects were evaluated regarding sEPCR., Results: At baseline, there was no difference in sTM, sEPCR, TNF-alpha and C-reactive protein (CRP) between the groups. In paired analysis, sEPCR (266 ± 132 to 117 ± 72 ng/ml), sTM (635 ± 165 to 100 ± 41 ng/ml) and TNF-alpha (11.2 ± 4.3 to 6.0 ± 3.5 pg/ml) were significantly decreased in RTx patients (P < 0.0001) at 3 months, while there was no change in the HD group. In the healthy subjects, sEPCR was found to be 79 ± 26 ng/ml at baseline, which was lower than in both groups., Conclusions: We showed that the recently proposed endothelial damage biomarkers, sTM and sEPCR, are elevated in HD patients and significantly decrease after kidney transplantation.

Renal infarction is a rare cause of acute abdominal and flank pain. Whether it occurs due to thrombosis or embolism, the occlusion of the renal arteries always results in renal infarction. Cigarette smoking is a known risk factor for arterial thrombosis. Both vasoconstrictor and pro-thrombotic effects of smoking lead to arterial thrombosis. Herein, we report a case of acute renal infarction in a heavy smoker. The definite diagnosis was made by contrast-enhanced abdominal computerized tomography and renal arteriography.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and serositis. The most important complication of FMF is renal amyloidosis, which determines the prognosis. The gene coding the disease (MEFV) is identified on the 16th chromosome. The most common MEFV mutations are M694V, M680I, V726A and M694I located on exon 10 and E148Q located on exon 2. Unfortunately, genotype-phenotype correlation is not well established and there are unexplained ethnic differences in amyloidosis rates. We report two sisters with a common genotype (M694V/M694V) presenting with different phenotypic characteristics: one complaining of intermittent abdominal pain, arthritis and fever, while the other was suffering from intermittent pleuritis and fever during attacks. The observation of different phenotypic presentations with a common genotype in two family members shows that different phenotypes cannot be explained by particular mutations. To understand the correlation between genotypic and phenotypic FMF variants the existence of complex alleles, modifier loci, genetic heterogeneity and possible epigenetic factors should be studied extensively.

Idiopathic retroperitoneal fibrosis (RF) is a histologically benign, nonspecific inflammatory process of the fibroadipose tissue in the retroperitoneum with an unknown etiology. It may be complicated due to encasement and obstruction of the retroperitoneal structures. Tamoxifen has been known to be an effective agent in regression of desmoid tumors which include similar mesenchymal elements to those seen in RF. Herein, we reported a case of RF presented with ureteral obstruction and acute renal failure. The patient was successfully treated with tamoxifen.

Background: Cyclic variation of myocardial-integrated backscatter (CV-IB) offers a non-invasive myocardial contractile performance assessment. There is limited data concerning CV-IB in end-stage renal disease (ESRD) patients., Methods: Forty essential hypertensive (EH) patients (mean age 51+/-8 yrs) and 24 ESRD patients (mean age 49+/-14 yrs) were compared to 10 healthy controls (mean age 45+/-10 yrs). A 2D-Doppler echocardiography with digitized imaging was performed to characterize myocardial ultrasonic tissue by CV-IB between systole and diastole at the interventricular septum (IVS) and left ventricular (LV) posterior wall (PW)., Results: There was no significant difference between age and sex among groups. Systolic and diastolic blood pressures (BP) were both higher in EH patients (157/96 mmHg in EH, 129/81 mmHg in ESRD and 115/77 mmHg in controls, p<0.001). Left ventricular mass index (LVMI) was higher in EH and ESRD patients than in controls (respectively, 119+/-37, 130+/-46, 87+/-12 g/m2, p<0.05), while there was no significant difference found between EH and ESRD patients. EH patient CV-IB values were significantly lower than in ESRD patients and controls (respectively, 6.9+/-1.6, 8.6+/-0.7, 10.6+/-1.1 dB, p<0.001 for IVS, 7.7+/-1.3, 8.7+/-0.8, 10.4+/-1.1 dB, p<0.001 for PW). CV-IB for PW and IVS were significantly lower in ESRD patients than in controls (p<0.001)., Conclusions: CV-IB can offer useful parameters for myocardial structure in EH and ESRD patients. Further studies are needed to clarify CV-IB in ESRD patients.

Diabetes mellitus is one of the major causes of chronic renal failure. Typical findings of diabetic nephropathy are early hyperfiltration followed by microalbuminuria and overt proteinuria, resulting in a progressive decrease in glomerular filtration rate. Rapidly progressive glomerulonephritis has rarely been reported in patients with diabetes mellitus. Here, we describe a patient with MPO-ANCA-associated vasculitis, presenting with pulmonary-renal syndrome. Immunosuppressive treatment, including pulse methyl-prednisolone and cyclophosphamide, was administered and the disease was resolved.

Nephrotic syndrome has been rarely reported after hematopoietic stem cell transplantation. We report a patient who developed nephrotic syndrome after allogeneic peripheral blood stem cell transplantation for acute myelogenous leukemia. Renal biopsy was performed and immunofluorescence and light microscopy were compatible with minimal change disease. The patient was treated with cyclophosphamide and prednisolone. Complete remission was achieved after three months. Previous reported cases are discussed.

Acute renal failure secondary to bilateral ureteral obstruction in pregnancy is rare. We describe a case of acute renal failure secondary to bilateral ureteral obstruction. A 27 year-old woman at 35 weeks' gestation was referred to our hospital with a diagnosis of acute renal failure. The patient had been well until four days earlier, when she developed an abrupt anuria. She had been administrated excessive amounts of fluids, and unresponsive to parenteral furosemide. She had mild pitting oedema and an S3 gallop with crackles in the lungs. The uterus was enlarged to the expected size with a cervical dilatation of 2 cm in diameter. Her serum creatinine level was 7.0 mg/dl. Renal ultrasound showed bilateral hydronephrosis of severe degree. The patient was immediately hemodialyzed for advanced renal failure with hypervolemia, and a healthy infant was born at the third hour of the HD session without any complication. On the next day, her urine volume was 200 ml/day and serum creatinine level was 6.8 mg/dl. For this reason, the patient underwent cystoscopy and ureteral stents were inserted bilaterally. There was no evidence of ureteral stones or obstructive lesions. After the stenting, the urine volume increased and serum creatinine was decreased gradually to normal level at the seventh day of postpartum. Two weeks later ureteral stents were removed and both infant and patient were completely healthy. To the best of our knowledge, this is the first case of delivery of an infant during a haemodialysis session.

Background: Carotid artery intima-media thickness (CIMT) has been used as a marker of atherosclerosis. An insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with various cardiovascular diseases. This study is aimed at evaluating early atherosclerotic involvement of carotid vessels and the relation to known risk factors and ACE gene I/D in hemodialysis (HD) patients., Methods: We measured CIMT using high-resolution B-mode ultrasonography in 51 non-diabetic HD patients and in 70 age- and sex-matched healthy controls, and evaluated the factors influencing CIMT. An I/D polymorphism in intron 16 of the gene coding for ACE was analysed by polymerase chain reaction., Results: The mean CIMT was significantly higher in HD patients than in healthy subjects (p<0.0001). In multiple regression analysis, independent risk factors for increased CIMT in HD patients were predialysis systolic blood pressure (p<0.001) and ACE D allele (p<0.01)., Conclusions: The present data suggest that CIMT is enlarged in HD patients. The ACE gene seems to be a candidate for influencing the CIMT and might therefore be involved in an HD patient's predisposition to the development of atherosclerosis.