The results of SGLT-2 inhibitors use in kidney transplantation: 1-year experiences from two centers.

PURPOSE: Sodium-glucose co-transporter-2 inhibitor (SGLT-2i) administration is associated with some concerns in regard to the increased risk of genital and urinary tract infections (UTI) in kidney transplant recipients (KTR). In this study, we present the results of SGLT-2i use in KTR, including the early post-transplant period. METHODS: Participants were divided into two groups: SGLT-2i-free diabetic KTR (Group 1, n = 21) and diabetic KTR using SGLT-2i (Group 2, n = 36). Group 2 was further divided into two subgroups according to the posttransplant prescription day of SGLT-2i; < 3 months (Group 2a) and ≥ 3 months (Group 2b). Groups were compared for development of genital and urinary tract infections, glycated hemoglobin a1c (HgbA1c), estimated glomerular filtration rate (eGFR), proteinuria, weight change, and acute rejection rate during 12-month follow-up. RESULTS: Urinary tract infections prevalence was 21.1% and UTI-related hospitalization rate was 10.5% in our cohort. Prevalence of UTI and UTI-related hospitalization, eGFR, HgbA1c levels, and weight gain were similar between the SGLT-2i group and SGLT-2i-free group, at the 12-month follow-up. UTI prevalence was similar between groups 2a and 2b (p = 0.871). No case of genital infection was recorded. Significant proteinuria reduction was observed in Group 2 (p = 0.008). Acute rejection rate was higher in the SGLT-2i-free group (p = 0.040) and had an impact on 12-month follow-up eGFR (p = 0.003). CONCLUSION: SGLT-2i in KTR is not associated with an increased risk of genital infection and UTI in diabetic KTR, even in the early posttransplant period. The use of SGLT-2i reduces proteinuria in KTR and has no adverse effects on allograft function at the 12-month follow-up.

COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic.

BACKGROUND: Kidney transplant recipients have an increased risk of complications from COVID-19. However, data on the risk of allograft damage or death in kidney transplant recipients recovering from COVID-19 is limited. In addition, the first and second waves of the pandemic occurred at different times all over the world. In Turkey, the Health Minister confirmed the first case in March 2020; after that, the first wave occurred between March and August 2020; afterward, the second wave began in September 2020. This study aims to demonstrate the clinical presentations of kidney transplant recipients in the first two waves of the pandemic in Turkey and explore the impact of COVID-19 on clinical outcomes after the initial episode. METHODS: Patients with COVID-19 from seven centers were included in this retrospective cohort study. Initially, four hundred and eighty-eight kidney transplant recipients diagnosed with COVID-19 between 1 March 2020 to 28 February 2021 were enrolled. The endpoints were the occurrence of all-cause mortality, acute kidney injury, cytokine storm, and acute respiratory distress syndrome. In addition, longer-term outcomes such as mortality, need for dialysis, and allograft function of the surviving patients was analyzed. RESULTS: Four hundred seventy-five patients were followed up for a median of 132 days after COVID-19. Forty-seven patients (9.9%) died after a median length of hospitalization of 15 days. Although the mortality rate (10.1% vs. 9.8%) and intensive care unit admission (14.5% vs. 14.5%) were similar in the first two waves, hospitalization (68.8% vs. 29.7%; p < 0.001), acute kidney injury (44.2% vs. 31.8%; p = 0.009), acute respiratory distress syndrome (18.8% vs. 16%; p = 0.456), and cytokine storm rate (15.9% vs. 10.1%; p = 0.072) were higher in first wave compared to the second wave. These 47 patients died within the first month of COVID-19. Six (1.4%) of the surviving patients lost allografts during treatment. There was no difference in the median serum creatinine clearance of the surviving patients at baseline (52 mL/min [IQR, 47-66]), first- (56 mL/min [IQR, 51-68]), third- (51 mL/min [IQR,48-67]) and sixth-months (52 mL/min [IQR, 48-81]). Development of cytokine storm and posttransplant diabetes mellitus were independent predictors for mortality. CONCLUSIONS: Mortality remains a problem in COVID-19. All the deaths occur in the first month of COVID-19. Also, acute kidney injury is common in hospitalized patients, and some of the patients suffer from graft loss after the initial episode.

Middle-term outcomes in renal transplant recipients with COVID-19: a national, multicenter, controlled study.

Background: In this study, we evaluated 3-month clinical outcomes of kidney transplant recipients (KTR) recovering from COVID-19 and compared them with a control group. Method: The primary endpoint was death in the third month. Secondary endpoints were ongoing respiratory symptoms, need for home oxygen therapy, rehospitalization for any reason, lower respiratory tract infection, urinary tract infection, biopsy-proven acute rejection, venous/arterial thromboembolic event, cytomegalovirus (CMV) infection/disease and BK viruria/viremia at 3 months. Results: A total of 944 KTR from 29 different centers were included in this study (523 patients in the COVID-19 group; 421 patients in the control group). The mean age was 46 ± 12 years (interquartile range 37-55) and 532 (56.4%) of them were male. Total number of deaths was 8 [7 (1.3%) in COVID-19 group, 1 (0.2%) in control group; P = 0.082]. The proportion of patients with ongoing respiratory symptoms [43 (8.2%) versus 4 (1.0%); P < 0.001] was statistically significantly higher in the COVID-19 group compared with the control group. There was no significant difference between the two groups in terms of other secondary endpoints. Conclusion: The prevalence of ongoing respiratory symptoms increased in the first 3 months post-COVID in KTRs who have recovered from COVID-19, but mortality was not significantly different.

Sequential Liver, Kidney, and Autologous Stem Cell Transplant for AL Amyloidosis: A Case Report.

AL type amyloidosis is a systemic disease characterized by the accumulation of amyloid fibrils that can affect many organs such as the skin, gastrointestinal tract, heart, lungs, liver, and kidney. The most frequently involved organ in amyloidosis is the kidney, but cardiac amyloidosis with the poor prognosis is amyloid organ involvement. In this study, we present the treatment of a 40-year-old female patient with acute Budd-Chiari syndrome and very severe proteinuria with sequential liver, kidney, and autologous stem cell transplant after the diagnosis of systemic amyloidosis. To reduce the effects of massive proteinuria and very severe hypoalbuminemia, bilateral renal artery embolization was performed first. After the evaluation of the patient, she underwent liver transplant from a deceased donor, and then kidney transplant was performed from her son 1 month later. Afterward, the patient was discharged without any problems and underwent chemotherapy and stem cell transplant for primary AL amyloidosis. She was followed up without any problem in terms of liver, kidney, and stem cell at the 24th postoperative month. This case shows that autologous stem cell transplant after kidney and liver transplant may be a good treatment option in a selected patient with stem cell involvement diagnosed as having AL amyloidosis.

COVID-19 Disease in a Kidney Transplant Recipient With Diffuse Intrarenal Hemorrhage.

Presentation of COVID-19 in renal transplant recipients is similar to that shown in the nonimmunocompromised population; almost all recipients who have this disease present with symptoms of the respiratory system. Acute kidney injury has been found prevalent in transplant recipients with COVID-19. In those with severe COVID-19 disease who transfer to an intensive care unit prevalence of acute kidney injury is more than 50%. The pathophysiological mechanisms of kidney involvement and the type of involvement are unclear. Here, we present a 71-year-old kidney transplant recipient who was admitted to our hospital with pulmonary and renal involvement. A kidney allograft biopsy demonstrated diffuse intrarenal hemorrhage, capillary congestion, and severe acute tubular injury. COVID-19 RNA was detected by real-time polymerase chain reaction from lysed allograft tissues, but no findings of acute or chronic cellular or antibody-mediated rejection were detected. This case indicates that COVID-19 may involve the allograft by causing hemorrhage within the renal parenchymal via direct or indirect pathways.

Risk Factors, Diagnosis, and Treatment of Lymphocele After Renal Transplantation: A Retrospective Study.

INTRODUCTION: Despite recent advances, lymphoceles are the most frequent complications following renal transplantation (RT), with an incidence of 0.6% to 51%. In this study, we present risk factors, treatments, and outcomes for lymphoceles after RT at our center. MATERIAL AND METHODS: Since January 2018, 461 RTs were performed at our center. Nine recipients were excluded. The remaining 452 RTs were analyzed retrospectively. Recipients were divided into 2 groups: a lymphocele group (n = 29) and a nonlymphocele group (n = 423). Lymphoceles were diagnosed by ultrasound. Statistical analyses were made using the SPSS 15 software program. RESULTS: Twenty-nine (6.4%) of the 452 recipients developed lymphoceles. Seven of these 29 (24.1%) recipients were asymptomatic. The most common symptom was hydronephrosis (34.4%). Percutaneous drainage was performed in 21 recipients; sclerotherapy with percutaneous drainage was used in the remaining 8. In 5 (17.2%) recipients, there was a recurrence of lymphoceles. There were significant differences with respect to age (50-65 years; P = .016), use of a drainage catheter (P = .044), and polycystic kidney diseases (P = .049). CONCLUSION: Lymphoceles can be treated successfully using the percutaneous drainage technique alone or in combination with povidone iodine. Drainage use, polycystic kidney disease, and age (50-65 years) were established as risk factors for lymphocele development.

Grafts With Multiple Renal Arteries in Kidney Transplantation.

BACKGROUND: Renal grafts with multiple renal arteries (MRA) are a compelling issue in surgery of kidney transplantation. Transplantations using "grafts with MRA" have conflicting results. Here, we present our experiences on the issue. METHOD: This is a single-center, observational, descriptive study. One hundred ninety-nine patients with end-stage renal disease received a kidney graft from their living- or deceased-related donors in our center between July 2016 and May 2017. We included all recipients to the study. Patients were divided into the following 2 groups: Group 1, recipients who received a renal graft with single renal artery, and Group 2, recipients who received a renal graft with MRA. Groups were compared for estimated glomerular filtration rates (months 1-3 and 12), delayed graft function, and graft survival. Data were analyzed by using SPSS for Windows version 15. RESULTS: One hundred ninety-five recipients with all documented data were analyzed. Graft function was compared between 2 groups in months 1, 3, and 12 and found both to have similar outcomes. MRA has been indicated to have no impact on delayed graft function, higher risk for vascular injury, and biopsy-proven acute tubular necrosis. Also, anastomosis sides have been found to have no importance on graft function in recipients with MRA (P > .05 between all sides). CONCLUSION: Our study indicates grafts with MRA and grafts with a single renal artery have comparable results in the first post-transplant year.

COVID-19 in kidney transplant recipients: A multicenter experience in Istanbul.

INTRODUCTION: Management of COVID-19 in kidney transplant recipients should include treatment of the infection, regulation of immunosuppression, and supportive therapy. However, there is no consensus on this issue yet. This study aimed to our experiences with kidney transplant recipients diagnosed with COVID-19. MATERIAL AND METHODS: Kidney transplant recipients diagnosed with COVID-19 from five major transplant centers in Istanbul, Turkey, were included in this retrospective cohort study. Patients were classified as having moderate or severe pneumonia for the analysis. The primary endpoint was all-cause mortality. The secondary endpoints were acute kidney injury, the average length of hospital stay, admission to intensive care, and mechanical ventilation. RESULTS: Forty patients were reviewed retrospectively over a follow-up period of 32 days after being diagnosed with COVID-19. Cough, fever, and dyspnea were the most frequent symptoms in all patients. The frequency of previous induction and rejection therapy was significantly higher in the group with severe pneumonia compared to the moderate pneumonia group. None of the patients using cyclosporine A developed severe pneumonia. Five patients died during follow-up in the intensive care unit. None of the patients developed graft loss during follow-up. DISCUSSION: COVID-19 has been seen to more commonly cause moderate or severe pneumonia in kidney transplant recipients. Immunosuppression should be carefully reduced in these patients. Induction therapy with lymphocyte-depleting agents should be carefully avoided in kidney transplant recipients during the pandemic period.

Combination of High-Dose Intravenous Cyclosporine and Plasma Exchange Treatment Is Effective in Post-Transplant Recurrent Focal Segmental Glomerulosclerosis: Results of Case Series.

BACKGROUND: Idiopathic focal segmental glomerulosclerosis (FSGS) commonly recurs in the early post-transplant period. The treatment protocols and results are conflictive in recurrent FSGS. We aimed to present the results of our treatment protocol and basic approach to the disease recurrences. METHODS: This prospective, single-center study was conducted between the years 2015 and 2018. Twelve patients who fit completely the diagnosis of idiopathic FSGS by clinical, laboratory, and biopsy findings were included. A specific treatment protocol which consists of plasma exchange and high dose intravenous cyclosporine was delivered to the patients independently of induction protocols. Twenty-four months of outcomes of graft functions were evaluated. RESULTS: Nine patients completed the treatment protocol and were documented for evaluation. All patients achieved a complete or partial remission in an average 24 months of follow-up period. CONCLUSION: Idiopathic FSGS is more commonly recurrent than thought to be. The early detection of proteinuria is crucial because the administration of a plasma exchange-based treatment protocol can reverse proteinuria. We think our treatment protocol is a well-established, efficient, and safe choice for post-transplant recurrent FSGS in adults.

Fabry Disease Prevalence in Renal Replacement Therapy in Turkey.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from lack of alpha-galactosidase A (AGALA) activity in lysosomes. OBJECTIVE: In this multicenter study, we aimed to evaluate the prevalence of FD in renal transplant (Tx) recipients in Turkey. We also screened dialysis patients as a control group. METHODS: All Tx and dialysis patients were screened regardless of the presence of a primary disease. We measured the AGALA activity in all male patients as initial analysis. Mutation analysis was performed in male patients with decreased AGALA activity and in female patients as the initial diagnostic assay. RESULTS: We screened 5,657 patients. A total of 17 mutations were identified. No significant difference was observed between the groups regarding the prevalence of patients with mutation. We found FD even in patients with presumed primary kidney diseases. Seventy-one relatives were analyzed and mutation was detected in 43 of them. We detected a patient with a new, unknown mutation (p.Cys223) in the GLA gene. CONCLUSIONS: There are important implications of the screening. First, detection of the undiagnosed patients leads to starting appropriate therapies for these patients. Second, the transmission of the disease to future generations may be prevented by prenatal screening after appropriate genetic counseling. In conclusion, we suggest screening of kidney Tx candidates for FD, regardless of etiologies of chronic kidney disease.

Endothelial nitric oxide synthase polymorphism influences renal allograft outcome.

BACKGROUND: Atherosclerotic lesions within the graft are considered to be a major cause of interstitial fibrosis/tubular atrophy (IF/TA). We evaluated the factors that influence the development of IF/TA and three- and five-yr graft survival including nitric oxide synthase (eNOS) and angiotensin II type 1 and type 2 receptor gene polymorphism. METHODS: Seventy-one male and 35 female patients (age: 34.9 ± 11.2 yr) who underwent living-related renal transplantation were included. Angiotensin type 1 and type 2 receptor gene polymorphisms and eNOS intron 4 gene polymorphism were analyzed. The pre- and post-transplant laboratory data, patient characteristics, acute rejection episodes, and presence of IF/TA were evaluated. RESULTS: Patients with the bb allele of eNOS gene had a lower prevalence of post-transplant third year (12.6% and 38.5%, p = 0.005) and fifth year IF/TA (46.6% and 82.3%, p = 0.02) and a lower incidence of five-yr graft failure (35.4% and 55.6%, p < 0.005). The eNOS gene polymorphism was independent and was the most prominent factor associated with third and fifth year IF/TA (p = 0.01, RR: 29.72, and p = 0.03, RR: 4.1, respectively). No significant relationship existed when angiotensin II gene polymorphisms were considered. CONCLUSIONS: We concluded that recipient eNOS gene polymorphism can predict IF/TA, and the presence of the bb allele is associated with better graft outcome.

Adherence, depression and quality of life in patients on a renal transplantation waiting list.

To study nonadherence, and its relationship with depression and quality of life (QOL) in patients on a cadaveric renal transplantation waiting list (RTWL). In 86 RTWL patients (56 men/30 women), there were 49 nonadherent patients (age, 46.8 +/- 21.8 years) and 37 adherent patients (age, 42.8 +/- 12.1 years). Clinical nonadherence was defined as skipping or shortening dialysis sessions, interdialytic weight gain (IDWG) of >5.7% body weight, a predialysis potassium level of >6 mEq/l and a predialysis phosphate level of >7.5 mg/dl. For each study subject, marital status, level of education duration of dialysis, prior renal transplantation, IDWG, predialysis blood urea nitrogen (BUN) value and creatinine, potassium, phosphate levels were recorded as were scores from the short form-36 and Beck depression inventory (BDI). A high IDWG (33.7% of the subjects) was the most common nonadherence pattern noted. Age, sex, marital status, duration of dialysis, prior transplantation, comorbid conditions the predialysis BUN values, the levels of creatinine, potassium, and phosphate were not significantly different between the two groups (P > 0.05). The level of education was higher in adherent group (P = 0.018). QOL and BDI scores were negatively correlated (P = 0.001, r = -0.561). Nonadherent patients had lower QOL (P = 0.04) and higher depression scores (P = 0.01) than did adherent patients. Of the depressed patients, 77.8% had a comorbid condition. Nonadherence was only associated with BDI scores (OR, 2.146; CI, 2.052-2.350; P = 0.002). In dialysis patients, close monitoring of adherence, early diagnosis of depression, and the treatment of disease may further enhance QOL during the waiting period for a cadaveric renal transplant.

Prevalence and predictors of arrhythmia in end stage renal disease patients on hemodialysis.

BACKGROUND: Sudden death is common in end-stage renal disease (ESRD). Cardiac arrhythmia is observed frequently in patients with ESRD and is thought to be responsible for this high rate of sudden death. This study investigated the prevalence and the predictors of arrhythmia in patients on maintenance dialysis. METHODS: Ninety-four patients on hemodialysis program were enrolled in the study. Routine laboratory results were noted. Arrhythmia, periods of silent ischemia, and heart-rate variability analyses were obtained from 24-hour Holter monitor recordings. Corrected QT (QTc) dispersion was calculated from 12-lead surface EKG. Echocardiographic and tissue Doppler examinations were performed on interdialytic days as well. Ventricular arrhythmia was classified according to Lown classification; classes 3 and above were accepted as complex ventricular arrhythmia (CVA). RESULTS: The mean age was 52.5+/-13.2 years; 44 (46.8%) were women. Ventricular premature contractions were detected in 80 (85.1%) patients, of whom 35 (37.2%) were classified as complex ventricular arrhythmia (CVA). Coronary artery disease, hypertension, and QTc dispersion appeared as independent factors predictive of CVA development. Atrial premature contractions (APC) were detected in 53 patients (56.4%) and supraventricular arrhythmia in 15 (16%) patients; all were identified as atrial fibrillation. Duration of dialysis therapy was found as an independent predictor of APC. CONCLUSION: Arrhythmia is frequently observed in ESRD patients receiving hemodialysis and may be responsible for the high rate of sudden mortality. Hypertension, CAD, and QTc dispersion are independent predictors of CVA, and duration of dialysis therapy is an independent factor affecting APC development in these patients.

Effects of ACE gene polymorphism on vitamin D therapy according to parathyroid hormone level in patients on hemodialysis.

Medical management is still far from optimal in secondary hyperparathyroidism. This may be explained, at least in part, by genetic differences. The aim of this study was to evaluate the association of genetic influences of angiotensinconverting enzyme (ACE) gene polymorphisms with response to vitamin D therapy among patients on hemodialysis (HD). Eighty-two patients (female/male, 34/48; mean age, 47.5+/-15.3 y; HD duration time, 76.6+/-33.2 mo) with endstage renal disease who were on maintenance HD were included in the study. Five-year retrospective demographic, clinical, laboratory, and treatment data (5-y cumulative doses of phosphate-binding drugs and oral and intravenous cumulative doses of active vitamin D) were retrieved from patients' hospital records. ACE gene polymorphisms of patients were documented and were used to group patients as follows: The insertion/deletion polymorphism group (I/D) consisted of (1) group non-DD (n=43), who had the DI or II allele, and (2) group DD (n=39), who had the DD allele. Patients with the DD allele (group DD) of ACE gene polymorphism had (1) significantly elevated mean 5-y intact parathyroid hormone levels when compared with the non-DD group (P=.009), and (2) significantly elevated oral and intravenous 5-y cumulative doses of vitamin D. Oral and intravenous 5-y cumulative doses of vitamin D used in group DD patients were significantly higher than those in group I patients (P=.038 and P=.037, respectively). Knowledge of genetic differences among patients on HD may be useful to the clinician in planning treatment strategy. ACE gene polymorphism may have an effect on hyperparathyroidism, as is seen in patients on HD. Patients from this group who have resistant hyperparathyroidism may be candidates for ACE inhibitor therapy.

Pulmonary function in uremic patients on long-term hemodialysis.

Twenty patients with end-stage renal failure who were on maintenance hemodialysis (HD) underwent pulmonary function testing (PFT) before and shortly after an HD session. On pre-HD PFT, the mean values of all parameters except residual volume (RV) were in the normal range. Mean RV was high (152.9%), and mean diffusing capacity of the lung for carbon monoxide (DLCO) was high-normal (110.4%). The pre-HD static inspiratory (PImax) and expiratory pressures (PEmax) were much lower than normal (67.4% and 36.3%, respectively). After the HD session, repeat PFT revealed a small increase in expiratory flow rates, and a significant drop in PImax. There was a strong correlation between PImax and PEmax (r=0.567, p<0.01) at the pre- and post-HD stages, indicating that common mechanism(s) are responsible for impairment of both inspiratory and expiratory muscle strength. The well-preserved DLCO was thought to be due to the use of biocompatible dialyzer membranes. Chronic vascular congestion might be the other explanation of high DLCO.