Biopsy-proven BK virus nephropathy in renal transplant recipients: A multi-central study from Turkey (BK-TURK STUDY).

AIM: BK polyomavirus infection is a challenging complication of renal transplantation. The management is not standardized and is based on reports from transplantation centers' experiences, usually with small sample sizes. Therefore, we aimed to present our countrywide experience with BK virus nephropathy (BKVN) in renal transplant recipients. MATERIALS AND METHODS: Our study was carried out with the participation of 30 transplantation centers from all regions of Turkey. Only cases with allograft biopsy-proven BKVN were included in the study. RESULTS: 13,857 patients from 30 transplantation centers were screened, and 207 BK nephropathy cases were included. The mean age was 46.4 ±  13.1 years, and 146 (70.5%) patients were male. The mean time to diagnosis of BK nephropathy was 15.8 ± 22.2 months after transplantation. At diagnosis, the mean creatinine level was 1.8 ±  0.7 mg/dL, and the mean estimated glomerular filtration rate was 45.8 ± 19.6 mL/min/1.73m2. In addition to dose reduction or discontinuation of immunosuppressive drugs, 18 patients were treated with cidofovir, 11 patients with leflunomide, 17 patients with quinolones, 15 patients with intravenous immunoglobulin (IVIG), 5 patients with cidofovir plus IVIG, and 12 patients with leflunomide plus IVIG. None of the patients receiving leflunomide or leflunomide plus IVIG had allograft loss. During follow-up, allograft loss occurred in 32 (15%) out of 207 patients with BK nephropathy. CONCLUSION: BKVN is still a frequent cause of allograft loss in kidney transplantation and is not fully elucidated. The results of our study suggest that leflunomide treatment is associated with more favorable allograft outcomes.

Thromboembolic complications after COVID-19 in kidney transplant recipients.

AIM: Increased venous thrombosis and arterial embolism rates are observed in the general population during or after COVID-19. Data regarding the kidney transplant population are scarce. In this study, we aim to investigate the thrombotic complications and risk factors associated with thrombotic complications in kidney transplant patients. METHODS: This retrospective observational study included adult kidney transplant recipients diagnosed with COVID-19 between March 2020 and June 2022. The endpoint was the occurrence of thromboembolic events. RESULTS: Four hundred and sixty-nine patients were followed for a median of 10.8 months after COVID-19. Forty patients (8.5%) died. Thromboembolic complications developed in 51 (11.9%) of the surviving patients. Twenty-four patients with thromboembolic events were receiving prophylactic anticoagulation before the event. The patients with mild, moderate, and severe COVID-19 were 292, 129, and 48, respectively. Patients with moderate COVID-19 had a significantly higher percentage of thromboembolic complications than patients with mild COVID-19. Older age, prior heart disease, and moderate COVID-19 were significantly associated with thromboembolic events. The incidence of thromboembolic events after COVID-19 is 10.9 per 100 patient-year. CONCLUSION: Thromboembolic complications were observed at increased rates in kidney transplant recipients after COVID-19. Therefore, prospective and cohort studies for post-COVID-19 complications regarding the treatment modalities are urgently needed.

Immunosuppressive treatment results in patients with primary IgA nephropathy in Turkiye; the data from TSN-GOLD working group.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) treatment consists of maximal supportive care and, for high-risk individuals, immunosuppressive treatment (IST). There are conflicting results regarding IST. Therefore, we aimed to investigate IST results among IgAN patients in Turkiye. METHOD: The data of 1656 IgAN patients in the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases Study Group were analyzed. A total of 408 primary IgAN patients treated with IST (65.4% male, mean age 38.4 ± 12.5 years, follow-up 30 (3-218) months) were included and divided into two groups according to treatment protocols (isolated corticosteroid [CS] 70.6% and combined IST 29.4%). Treatment responses, associated factors were analyzed. RESULTS: Remission (66.7% partial, 33.7% complete) was achieved in 74.7% of patients. Baseline systolic blood pressure, mean arterial pressure, and proteinuria levels were lower in responsives. Remission was achieved at significantly higher rates in the CS group (78% vs. 66.7%, p = 0.016). Partial remission was the prominent remission type. The remission rate was significantly higher among patients with segmental sclerosis compared to those without (60.4% vs. 49%, p = 0.047). In the multivariate analysis, MEST-C S1 (HR 1.43, 95% CI 1.08-1.89, p = 0.013), MEST-C T1 (HR 0.68, 95% CI 0.51-0.91, p = 0.008) and combined IST (HR 0.66, 95% CI 0.49-0.91, p = 0.009) were found to be significant regarding remission. CONCLUSION: CS can significantly improve remission in high-risk Turkish IgAN patients, despite the reliance on non-quantitative endpoints for favorable renal outcomes. Key predictors of remission include baseline proteinuria and specific histological markers. It is crucial to carefully weigh the risks and benefits of immunosuppressive therapy for these patients.

Efficacy and safety of interleukin-1 blockers in kidney transplant recipients with familial Mediterranean fever: a propensity score-matched cohort study.

BACKGROUND: Data on use of interleukin (IL)-1 blockers in kidney transplant recipients (KTRs) with familial Mediterranean fever (FMF) are very limited. We aimed to evaluate the efficacy and safety of anakinra and canakinumab in the transplantation setting. METHODS: In this retrospective cohort study, we included KTRs who suffered from AA amyloidosis caused by FMF and treated with anakinra or canakinumab (study group, n = 36). Using propensity score matching, we selected 36 patients without FMF or amyloidosis from our database of 696 KTRs as the control group. Primary outcomes were patient and graft survival. Biopsy-confirmed graft rejection, changes in estimated glomerular filtration rate (eGFR), high-sensitivity CRP (hsCRP), erythrocyte sedimentation rate (ESR), proteinuria and number of monthly attacks were secondary outcomes. RESULTS: All KTRs with FMF began IL-1 blocker therapy with anakinra and nine (25%) were switched to canakinumab. Overall death was more frequent in the study group (19.4% vs 0%) (P = .005); however, overall graft loss was comparable between study (27.8%) and control groups (36.1%) (P = .448). Five- and 10-year graft survival rates were significantly higher in the study group (94.4% and 83.3%, respectively) than in the control group (77.8% and 63.9%, respectively) (P = .014 and P < .001, respectively). Rejections were numerically lower in study group (8.3% vs 25%), but it did not reach to statistical significance (P = .058). When compared with the pre-treatment period, with IL-1 blockers, the number of attacks per month (P < .001), and eGFR (P = .004), hsCRP (P < .001) and ESR (P = .026) levels were lower throughout the follow-up, whereas proteinuria levels were not. CONCLUSIONS: Anakinra and canakinumab are effective in KTRs suffering from FMF; however, the mortality rate may be of concern.

Outcomes of kidney transplantation in patients with congenital anomalies of the kidney and urinary tract: a propensity-score-matched analysis with case-control design.

BACKGROUND: We compared long-term outcomes after kidney transplantation (KTx) in patients with and without congenital anomalies of the kidney and urinary tract (CAKUT). METHODS: KTx recipients (KTRs) with CAKUT in 1980-2016 were identified; their hard copy and electronic medical records were reviewed and compared to a propensity-score-matched control group (non-CAKUT) from the same period. The primary outcomes were graft loss or death with a functioning graft; secondary outcomes included posttransplant urinary tract infections (UTIs) and biopsy-proven rejection (BPR). RESULTS: : We identified 169 KTRs with CAKUT and 169 matched controls. Median follow-up was 132 (IQR: 75.0-170.0) months. UTIs were more common in CAKUT patients compared to non-CAKUT group (20.7% vs 10.7%; p = 0.01). Rates of BPR were similar between the two groups. In Kaplan-Meier analysis, 10-year graft survival rates were significantly higher in the CAKUT group than in the non-CAKUT group (87.6% vs 69.2%; p < 0.001), while patient survival rates were similar. In multivariate Cox regression analyses, CAKUT (HR: 0.469; 95% CI: 0.320-0.687; p < 0.001) and PRA positivity before transplantation (HR: 3.756; 95% CI: 1.507-9.364; p = 0.005) predicted graft loss. DISCUSSION: Graft survival in KTRs with CAKUT appears superior to KTRs without CAKUT. Transplant centers should develop multidisciplinary educational and social working groups to support and encourage CAKUT patients with kidney failure to seek for transplants.

Long-Term Outcomes of Living-Related Kidney Donation for Alport Syndrome Spectrum: A Propensity Score-Matched Analysis.

INTRODUCTION: Data to guide the evaluation of living-related donor candidates for kidney transplant recipients with Alport syndrome (AS) spectrum are limited. We aimed to examine a cohort of living-related donors to recipients with AS and compare their outcomes with a control group to improve understanding of the clinical course and outcomes of living donation in this context. METHODS: Living donors (LDs) of AS recipients and propensity score-matched control LDs without any family history of AS (control group) were followed for major cardiac events, death, post-donation estimated glomerular filtration rate (eGFR), and proteinuria. RESULTS: There were 31 LDs (48.4% male), in whom relationship to AS recipient included mother (45.2%), father (32.3%), sibling (16.1%), grandparent (3.2%), and uncle (3.2%). Long-term outcomes over 10.0 (IQR, 3.0-15.0) years were evaluated in 25 and 25 LDs from study and control groups, respectively. During follow-up, 5 LDs (20.0%) in study group developed major cardiac event (acute coronary ischemia [n = 4] and severe congestive heart failure [n = 1]) after 5.5 (IQR, 4.5-10.3) years, whereas only 2 (8.0%) LDs in control group developed major cardiac events (p = 0.221). New-onset hypertension was higher in study group (56.0%) compared to the control group (16.0%) (p = 0.003). Three donors in study and 2 donors in control group who developed new-onset hypertension died during follow-up (p = 0.297). Major cardiac event rate was significantly higher in donors who developed hypertension after donation (0 vs. 28.0%, p < 0.001). There were no differences between study groups regarding last eGFR and proteinuria levels (p = 0.558 and p = 0.120, respectively). DISCUSSION/CONCLUSION: Although the risk of kidney disease can be minimized by careful donor evaluation, our findings suggest that hypertension risk after the donation is higher than expected in related donors of recipients with AS.

Genotype-Phenotype correlations of SCARB2 associated clinical presentation: a case report and in-depth literature review.

BACKGROUND: Biallelic pathogenic variants in the SCARB2 gene have been associated with action myoclonus-renal failure (AMRF) syndrome. Even though SCARB2 associated phenotype has been reported to include typical neurological characteristics, depending on the localization and the feature of the pathogenic variants, clinical course and the presentations have been shown to differ. CASE PRESENTATION: Whole exome sequencing (WES) analysis revealed a homozygous truncating variant (p.N45MfsX88) in SCARB2 gene in the index case, and subsequent sanger sequencing analysis validated the variant in all affected family members from a Turkish family with the clinical characteristics associated with AMRF and related disorders. Intrafamilial clinical heterogeneity with common features including dysarthria, tremor and proteinuria, and distinct features such as peripheral neuropathy (PNP), myoclonus and seizures between the affected cases, was observed in the family. In-depth literature review enabled the detailed investigation of the reported variants associated with AMRF and suggested that while the type of the variant did not have a major impact on the course of the clinical characteristics, only the C terminal localization of the pathogenic variant significantly affected the clinical presentation, particularly the age at onset (AO) of the disease. CONCLUSIONS: In this study we showed that biallelic SCARB2 pathogenic variants might cause a spectrum of common and distinct features associated with AMRF. Of those features while the common features include myoclonus (100%), ataxia (96%), tonic clonic seizures (82%), dysarthria (68%), tremor (65%), and renal impairment (62%), the uncommon features involve PNP (17%), hearing loss (6.8%), and cognitive impairment (13.7%). AO has been found to be significantly higher in the carriers of the p.G462DfsX34 pathogenic variant. SCARB2 pathogenic variants have not been only implicated in AMRF but also in the pathogenesis of Parkinson's disease (PD) and Gaucher disease (GD), suggesting the importance of genetic and functional studies in the clinical and the diagnostic settings. Given the proven role of SCARB2 gene in the pathogenesis of AMRF, PD and GD with a wide spectrum of clinical symptoms, investigation of the possible modifiers, such as progranulin and HSP7, has a great importance.

Efficacy of intravenous combined immunosuppression with plasmapheresis in adult patients with refractory primary focal segmental glomerulosclerosis.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) treatment is based on immunosuppressive therapies. Since refractory disease is common, alternative methods are emerging. One of these methods is plasmapheresis with intravenous cyclosporine and corticosteroids, and it could be an option in post-transplant recurrent FSGS. We retrospectively investigated the efficacy of this combined treatment in adult patients with refractory primary FSGS. METHODS: Seven refractory primary FSGS patients were included. Demographics, estimated glomerular filtration rates, serum albumin levels, urine protein/creatinine ratios, and previous treatments were evaluated. Also, complications and remission rates were assessed. RESULTS: Median patient age was 23 years. Median duration of diagnosis was 2 years. Median number of plasmapheresis sessions was 14. Five of seven patients (71.4%, one complete, four partial remissions) were responders after the protocol. Changes in serum albumin levels and proteinuria after protocol were statistically significant (P = 0.018 and P = 0.018, respectively). eGFR levels did not change statistically (P = 0.753). Median follow-up duration after the treatment was 17 months. However, two patients experienced disease relapse (28.5%). End-stage kidney disease was developed in two patients. Sustained remission rate was 42.8% during follow-up (One complete and two partial remissions). Also, 42.8% of patients experienced catheter infections. Catheter-associated thrombosis that required surgery was observed in a patient. CONCLUSIONS: Plasmapheresis combined with intravenous cyclosporine and corticosteroids could be an option in refractory primary FSGS. High response rates after this protocol were encouraging. However, the relapsing disease was observed after the cessation of apheresis. Also, complications of the protocol could limit the applicability.

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.

LIMS1 risk genotype and T cell-mediated rejection in kidney transplant recipients.

BACKGROUND: This study aims to examine the association of LIM zinc finger domain containing 1 (LIMS1) genotype with allograft rejection in an independent kidney transplant cohort. METHODS: We genotyped 841 kidney transplant recipients for the LIMS1 rs893403 variant by Sanger sequencing followed by polymerase chain reaction confirmation of the deletion. Recipients who were homozygous for the LIMS1 rs893403 genotype GG were compared with the AA/AG genotypes. The primary outcome was T cell-mediated or antibody-mediated rejection (TCMR or ABMR, respectively) and secondary outcome was allograft loss. RESULTS: After a median follow-up of 11.4 years, the rate of TCMR was higher in recipients with the GG genotype (n = 200) compared with the AA/AG genotypes (n = 641) [25 (12.5%) versus 35 (5.5%); P = 0.001] while ABMR did not differ by genotype [18 (9.0%) versus 62 (9.7%)]. Recipients with the GG genotype had 2.4 times higher risk of TCMR than those who did not have this genotype [adjusted hazard ratio2.43 (95% confidence interval 1.44-4.12); P = 0.001]. A total of 189 (22.5%) recipients lost their allografts during follow-up. Kaplan-Meier estimates of 5-year (94.3% versus 94.4%; P = 0.99) and 10-year graft survival rates (86.9% versus 83.4%; P = 0.31) did not differ significantly in the GG versus AA/AG groups. CONCLUSIONS: Our study demonstrates that recipient LIMS1 risk genotype is associated with an increased risk of TCMR after kidney transplantation, confirming the role of the LIMS1 locus in allograft rejection. These findings may have clinical implications for the prediction and clinical management of kidney transplant rejection by pretransplant genetic testing of recipients and donors for LIMS1 risk genotype.

Significance of caveolin-1 immunohistochemical staining differences in biopsy samples from kidney recipients with BK virus viremia.

BK virus infections which usually remains asymptomatic in healthy adults may have different clinical manifestations in immunocompromised patient population. BK virus reactivation can cause BK virus nephropathy in 8% of kidney transplant patients and graft loss may be seen if not treated. Clathrin or Caveolar system is known to be required for the transport of many viruses from Polyomaviruses family including BK viruses. In this study, kidney transplant patients with BK virus viremia were divided into two groups according to the BK virus nephropathy found in kidney biopsy (Group I: Viremia+, Nephropathy+ / Group II: Viremia+, Nephropathy-). Kidney biopsies were examined with immunohistochemical staining to determine the distribution and density of the Caveolin-1 and Clathrin molecules. Immunohistochemical staining of the 31 pathologic specimens with anti-caveolin-1 immunoglobulin revealed statistically significant difference between group-I and group-II. The number of the specimens stained with anti-caveolin-1 was less in group I. On the other hand, we did not find any difference between the groups regarding the anti-clathrin immunochemical analysis. According to these findings, caveolin-1 expression differences in kidney transplant patients may be important in disease progression.

Antibody response to two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) in kidney transplant recipients.

BACKGROUND: Coronavirus Disease-19 (COVID-19) has high mortality in kidney transplant recipients (KTR), and vaccination against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is vital for this population. Although the humoral response to messenger RNA vaccines was shown to be impaired in KTR, there is a lack of data regarding the antibody response to inactivated vaccines. We investigated the antibody response to two consequent doses of the inactivated SARS-CoV-2 vaccine (CoronaVac; Sinovac Biotech, China). METHODS: A total of 118 patients from two centers were included. The levels of anti-SARS-CoV-2 immunoglobulin-G antibodies against the nucleocapsid and spike antigens were determined with enzyme immunoassay (DIA.PRO; Milano, Italy) before the vaccine and one month after the second dose of the vaccine. Thirty-three patients were excluded due to antibody positivity in the serum samples obtained before vaccination. RESULTS: Eighty-five patients, 47 of whom were female, with a mean age of 46 ± 12, were included in the statistical analysis. The maintenance immunosuppressive therapy comprised tacrolimus (88.2%), mycophenolate (63.6%), and low-dose steroids (95.3%) in the majority of the patients. After a median of 31 days following the second dose of the vaccine, only 16 (18.8%) patients developed an antibody response. The median (IQR) antibody level was 52.5 IU/ml (21.5-96). Age (48 vs. 38, p = .005) and serum creatinine levels (1.14 vs. 0.91, p = .04) were higher in non-responders and were also found to be independently associated with the antibody response (odds ratio (OR): 0.93, p = 0.012 and 0.15, p = 0.045, respectively) in multivariate analysis. CONCLUSION: In this study, we found the antibody response to the inactivated vaccine to be considerably low (18.8%) in KTR. Increased age and impaired renal function were associated with worse antibody response. Based on the knowledge that mRNA vaccines yield better humoral responses, this special population might be considered for additional doses of mRNA vaccination.

Improving the urine spot protein/creatinine ratio by the estimated creatinine excretion to predict proteinuria in pediatric kidney transplant recipients.

BACKGROUND: Since the daily creatinine excretion rate (CER) is directly affected by muscle mass, which varies with age, gender, and body weight, using the spot protein/creatinine ratio (Spot P/Cr) follow-up of proteinuria may not always be accurate. Estimated creatinine excretion rate (eCER) can be calculated from spot urine samples with formulas derived from anthropometric factors. Multiplying Spot P/Cr by eCER gives the estimated protein excretion rate (ePER). We aimed to determine the most applicable equation for predicting daily CER and examine whether ePER values acquired from different equations can anticipate measured 24 h urine protein (m24 h UP) better than Spot P/Cr in pediatric kidney transplant recipients. METHODS: This study enrolled 23 children with kidney transplantation. To estimate m24 h UP, we calculated eCER and ePER values with three formulas adapted to children (Cockcroft-Gault, Ghazali-Barratt, and Hellerstein). To evaluate the accuracy of the methods, Passing-Bablok and Bland-Altman analysis were used. RESULTS: A statistically significant correlation was found between m24 h UP and Spot P/Cr (p < .001, r = 0.850), and the correlation was enhanced by multiplying the Spot P/Cr by the eCER equations. The average bias of the ePER formulas adjusted by the Cockcroft-Gault, Ghazali-Barratt, and Hellerstein equations were -0.067, 0.031, and 0.064 g/day, respectively, whereas the average bias of Spot P/Cr was -0.270 g/day obtained by the Bland-Altman graphics. CONCLUSION: Using equations to estimate eCER may improve the accuracy and reduce the spot urine samples' bias in pediatric kidney transplantation recipients. Further studies in larger populations are needed for ePER reporting to be ready for clinical practice.

The relationship between glomerular IgG staining and poor prognostic findings in patients with IgA nephropathy: the data from TSN-GOLD working group.

BACKGROUND: Galactose-deficient IgA1 (Gd-IgA1) has an increased tendency to form immunocomplexes with IgG in the serum, contributing to IgAN pathogenesis by accumulating in the glomerular mesangium. Several studies showed that glomerular IgG deposition in IgAN is an important cause of mesangial proliferation and glomerular damage. This study aims to determine the association of the positivity of IgG and the intensity of IgG staining with a poor renal prognosis. METHODS: A total of 943 IgAN patients were included in the study. Glomerular IgG staining negative and positive patients were compared using Oxford classification scores, histopathological evaluations, proteinuria, eGFR, albumin, blood pressures. IgG positive patients were classified as (+), (++), (+++) based on their staining intensity, and the association with the prognostic criteria was also evaluated. RESULTS: 81% (n = 764) of the patients were detected as IgG negative, while 19% (n = 179) were positive. Age, gender, body mass index, blood pressure, proteinuria, eGFR, uric acid values were similar in IgG positive and negative patients who underwent biopsy (p > 0.05). Intensity of glomerular IgG positivity was not found to be associated with diastolic and systolic blood pressure, urea, uric acid, age, eGFR, albumin, proteinuria (p > 0.05 for all, r = - 0.084, r = - 0.102, r = - 0.006, r = 0.062, r = 0.014, r = - 0.044, r = - 0.061, r = - 0.066, r = 0.150, respectively). There was no difference for histopathological findings between IgG (+), IgG (++), IgG (+++) groups (for all, p > 0.05). CONCLUSION: Glomerular IgG negativity and positivity detected by routine IFM in IgAN patients is not associated with poor renal prognostic risk factors.

Case report: A kidney transplant patient with mild COVID-19.

Coronavirus Disease 2019 (COVID-19) is currently a pandemic with a mortality rate of 1%-6% in the general population. However, the mortality rate seems to be significantly higher in elderly patients, especially those hospitalized with comorbidities, such as hypertension, diabetes, or coronary artery diseases. Because viral diseases may have atypical presentations in immunosuppressed patients, the course of the disease in the transplant patient population is unknown. Hence, the management of these patients with COVID-19 is an area of interest, and a unique approach is warranted. Here, we report the clinical features and our treatment approach for a kidney transplant patient with a diagnosis of COVID-19. We believe that screening protocols for SARS-Cov-2 should be re-evaluated in patients with solid-organ transplants.

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.

Epidemiological features of primary glomerular disease in Turkey: a multicenter study by the Turkish Society of Nephrology Glomerular Diseases Working Group.

BACKGROUND: The largest data on the epidemiology of primary glomerular diseases (PGDs) are obtained from the databases of countries or centers. Here, we present the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group. METHODS: Data of patients who underwent renal biopsy and received the diagnosis of PGD were recorded in the database prepared for the study. A total of 4399 patients from 47 centers were evaluated between May 2009 and May 2019. The data obtained at the time of kidney biopsy were analyzed. After the exclusion of patients without light microscopy and immunofluorescence microscopy findings, a total of 3875 patients were included in the study. RESULTS: The mean age was 41.5 ± 14.9 years. 1690 patients were female (43.6%) and 2185 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGD was IgA nephropathy (25.7%) followed by membranous nephropathy (25.6%) and focal segmental glomerulosclerosis (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. The mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. The median proteinuria, serum creatinine, estimated GFR, and mean albumin values were 3300 (IQR: 1467-6307) mg/day, 1.0 (IQR: 0.7-1.6) mg/dL, 82.9 (IQR: 47.0-113.0) mL/min and 3.2 ± 0.9 g/dL, respectively. CONCLUSIONS: The distribution of PGDs in Turkey has become similar to that in other European countries. IgA nephropathy diagnosed via renal biopsy has become more prevalent compared to membranous nephropathy.

Co-Deposition of IgM and C3 May Indicate Unfavorable Renal Outcomes in Adult Patients with Primary Focal Segmental Glomerulosclerosis.

BACKGROUND/AIMS: We aimed to investigate the effects of glomerular IgM and C3 deposition on outcomes of adult patients with primary focal segmental glomerulosclerosis (FSGS). METHODS: In this retrospective analysis, 86 consecutive adult patients with biopsy-proven primary FSGS were stratified into 3 groups according to their histopathological features: IgM- C3-, IgM+ C3-, and IgM+ C3+. Primary outcome was defined as at least a 50% reduction in baseline estimated glomerular filtration rate (eGFR) or development of kidney failure, while complete or partial remission rates were secondary outcomes. RESULTS: Glomerular IgM deposits were found in 44 (51.1%) patients, 22 (25.5%) of which presented with accompanying C3 deposition. Patients in IgM+ C3+ group had higher level of proteinuria (5.6 g/24 h [3.77-8.5], p = 0.073), higher percentage of segmental glomerulosclerosis (20% [12.3-27.2], p = 0.001), and lower levels of eGFR (69 ± 37.2 mL/min/1.73 m2, p = 0.029) and serum albumin (2.71 ± 0.85 g/dL, p = 0.045) at the time of diagnosis. Despite 86.3% of patients in IgM+ C3+ group (19/22) received immunosuppressive treatment, the primary outcome was more common in patients in the IgM+ C3+ group compared with patients in IgM+ C3- and IgM- C3- groups (11 [50%] vs. 2 [9%] and 11 [26.1%] respectively [p = 0.010]). Complete or partial remission rates were lower in patients in the IgM+ C3+ group (5/22, 22.7%), as well (p = 0.043). Multivariate Cox regression analysis revealed that IgM and C3 co-deposition was an independent risk factor associated with primary outcome (hazard ratio 3.355, 95% CI 1.349-8.344, p = 0.009). CONCLUSIONS: Glomerular IgM and C3 co-deposition is a predictor of unfavorable renal outcomes in adult patients with primary FSGS.

Re-evaluation of glomerulitis using occlusion criteria based on the Banff 2013 revision: a retrospective study.

The presence of occlusion/near-occlusion of glomerular capillaries was recently added to the existing definition of glomerulitis (g). We retrospectively re-evaluated 135 renal allograft biopsies regarding g to ensure no antibody-damaged grafts were missed. Previous and revised g scores (pg and rg, respectively) were compared for clinicopathologic correlations. The g score did not change in 100 (74.1%) biopsies. Thirty-five (25.9%) biopsies were changed to a lower score. Sensitivity and specificity of pg and rg for the presence of donor-specific antibodies (DSA) were 76% vs. 58% and 70% vs. 79%, respectively. Pg score indicated graft loss with 65% sensitivity and 63% specificity, whereas rg showed 46% sensitivity and 71% specificity. Area under the curve (AUC) values in ROC analysis for DSA and graft loss were as follows: pg, 0.773; rg, 0.693; and pg, 0.635; rg, 0.577, respectively. A comparison of the two AUC values revealed a significant difference between pg and rg only for DSA (P = 0.0076). Pg and post-transplant time of biopsy independently predicted graft loss, whereas rg did not. In conclusion, revised g scores showed lesser sensitivity but higher specificity for DSA and graft loss. Recent definition of g missed antibody-mediated rejection in few cases, and it was not an independent predictor for graft loss.

The effect of histopathologic and clinical features on allograft survival in renal transplant patients with antibody-mediated rejection.

BACKGROUND: Antibody-mediated rejection is a frequent cause of graft failure; however, prognostic indications of this complication have not been well defined. The aim of this study was to evaluate the association of histopathological and clinical features and to determine the effect of these findings on allograft survival in patients with AMR. METHODS: Fifty-two patients suffered from AMR (30 male; mean age 39 ± 11 years) were included in the study. Data were investigated retrospectively and graft survival was analyzed. All transplant biopsies were evaluated according to Banff 2009 classification. RESULTS: Of the 52 cases, 45 were transplanted from living-donors. Twenty-one patients were diagnosed in the first 3-months after transplantation. Graft survival was 65% at 12 months and 54% at 36 months. Mean serum creatinine at time of biopsy was 3.8 ± 3.6 mg/dL. Thirty-five of the 52 cases showed diffuse C4d positivity, 12 cases showed focal and 5 remained C4d negative. One of the patients died, 13 experienced graft loss and 38 survived with functioning grafts. Serum creatinine levels at time of biopsy were correlated with graft survival (p = .021: OR = 1.10: 95 % CI = 1.015-1.199). In terms of the impact of pathological findings; tubulitis (p=.007: OR = 2.62: 95 % CI = 1.301-5.276), intimal arteritis (p=.017: OR = 2.85: 95% CI = 1.205-6.744) and interstitial infiltration (p=.004: OR = 3.37: 95% CI = 1.465-7.752) were associated with graft survival. CONCLUSIONS: Serum creatinine at time of biopsy, tubulitis, intimal arteritis and interstitial infiltration were significantly associated with graft survival. Antibody-mediated rejection is associated with reduced long-term graft survival.