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.

Baseline inflammation indexes and neutrophil-to-LDH ratio for prediction of the first mobilization failure without plerixafor-based regimens in multiple myeloma and lymphoma patients: A single-center retrospective study.

BACKGROUND: Many factors were identified for mobilization failure (MF) in autologous hematopoietic stem-cell transplantation. To our knowledge, this is the first study to investigate the efficacy of baseline inflammation indexes and neutrophil-to-lactate dehydrogenase (LDH) ratio to predict MF in multiple myeloma (MM) and lymphoma. METHODS: A total of 240 patients with lymphoma or MM hospitalized between January 2014 and June 2022 for the first stem cell mobilization were included in this retrospective single-center study. We evaluated the impact of baseline demographic, clinical, and laboratory data (before granulocyte colony-stimulating factor and chemotherapy implementation), including neutrophil, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), neutrophil-to-C-reactive protein, and neutrophil-to-LDH ratios on MF. RESULTS: A total of 240 patients were divided into successful (214 patients, 89.16%) and poor mobilizers (26 patients, 10.84%). Poor mobilizers had lower neutrophil, NLR, SII, and neutrophil-to-LDH ratios (P values were .001, .022, .001, and .001, respectively). Among these markers, only the neutrophil-to-LDH ratio was statistically low in both poor mobilizer MM and lymphoma patients. Receiving operator characteristic curve analysis was performed to evaluate neutrophil, SII, and neutrophil-to-LDH ratios for MF. Neutrophil-to-LDH ratio had the highest specificity (93.93%, for ≤9.904 cut-off) compared to the other two variables. Multivariate logistic regression analysis showed that neutrophil-to-LDH ratio ≤ 9.904 (cut-off) (odds ratio: 7.116, P = .001), neutrophil counts ≤3300/mm3 (cut-off) (odds ratio: 3.248, P = .021), and lymphoma diagnosis (odds ratio: 2.674, P = .039) were independent risks for MF. CONCLUSION: The neutrophil-to-LDH ratio could be a novel marker in lymphoma and MM patients to predict the first MF. New studies should be conducted for the optimization of this index.

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.

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.

Chronic oxcarbazepine intoxication in a patient with primary antiphospholipid syndrome on maintenance haemodialysis.

WHAT IS KNOWN AND OBJECTIVE: Oxcarbazepine (OXC) is an antiepileptic drug. Patients suffering from chronic kidney disease with an estimated glomerular filtration rate below 30 ml/min/1.73 m2 require dose adjustments for OXC. CASE SUMMARY: A 31-year-old man was admitted with a history of diplopia, ataxia and dizziness attacks that had disappeared after a regular haemodialysis sessions for three months. Medical history was remarkable for primary antiphospholipid syndrome (APS). However, no signs of new-onset APS-related neurological involvement were present. Then, it was revealed that the patient had been using 2400 mg/day of OXC for four months, despite the prescription of half of this dose. Serum OXC level was 50 mcg/ml (reference: 3-35 mcg/ml) before a regular haemodialysis session. All symptoms disappeared in a few days after reducing to 1200 mg/day and never recurred. WHAT IS NEW AND CONCLUSION: We reported a chronic OXC intoxication in a patient on maintenance haemodialysis. To the best of our knowledge, it is the first chronic OXC intoxication case in the literature. It could be related to episodic removal of OXC and its metabolites via haemodialysis. Consequently, dose modification of drugs is a pivotal point in haemodialysis patients. Chronic drug intoxications must be kept in mind in haemodialysis patients with unexplained symptoms.

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.

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.

Concurrent Cobalamin C and Plasminogen Deficiencies in a Patient with Chronic Thrombotic Microangiopathy.

BACKGROUND: Although most patients with atypical hemolytic uremic syndrome (aHUS) have variants in genes participating in alternative complement pathways, rare variants in non-complement pathway-related genes, including DGKE, INF2, MMACHC, PLG, and THBD, have also been described. CASE PRESENTATION: We report an 18-year-old male patient with renal biopsy-proven chronic thrombotic microangiopathy that raised suspicion of aHUS. Whole-exome sequencing revealed a novel pathogenic homozygous MMACHC c.484G>T (p.Gly162Trp) variant. Subsequently, clinical and laboratory findings confirmed cobalamin C (Cbl C) deficiency. Also, homozygous missense c.1112C>T PLG (p.Thr371Ile) variant was detected (it had been reported as a variant of unknown significance). However, the low serum plasminogen (PLG) activity proved the pathogenicity of c.1112C>T. Hence, the patient was diagnosed with concurrent Cbl C and PLG deficiencies. Segregation analysis revealed that the mother and father had the same heterozygous PLG and MMACHC variants. PLG variants have generally been described in aHUS patients concomitant with complement gene variants in the literature; therefore, the association between aHUS and PLG variants is controversial. The possible contribution of PLG deficiency to thrombotic microangiopathy was also discussed in this case. CONCLUSION: Non-complement-mediated aHUS is an exceptional disorder. A limited number of genes are involved in this entity. To our knowledge, this is the first aHUS patient diagnosed with both Cbl C and PLG deficiencies in the literature.

LIM Zinc Finger Domain Containing 1 Risk Genotype of Recipient Is Associated with Renal Tubular Inflammation in Kidney Transplantation.

BACKGROUND: Homozygosity for LIMS1 rs893403-GG genotype is linked to an increased risk of allograft rejection after kidney transplantation. Ischemia-reperfusion of the kidney allograft leads to long term infiltration of activated and effector-memory T lymphocytes and resulting in rejection and long-term fibrosis. However, the genotype, LIMS1 expression under ischemic conditions and the long-term histopathological relationships remain ill-defined. METHODS: We examined the impact of the recipient's LIMS1-rs893403 genotype with transplant kidney histopathology. The association of the LIMS1-rs893403 genotype and LIMS1 and GCC2 mRNA expression in ischemic donor kidneys were also examined. Recipients who underwent transplant kidney biopsy were genotyped for the LIMS1-rs893403 variant and associated deletion. Histopathological findings were compared between recipients with LIMS1 risk and non-risk genotypes. Real-time PCR and immunofluorescence staining for LIMS1 and GCC2 expression were performed in non-utilized donor kidneys. RESULTS: Demographic, clinical, and treatment characteristics and the histopathological diagnosis were similar between recipients with rs893403 GG and AA/AG genotype. The Banff tubulitis score was higher in GG recipients (n = 24) compared to AA/AG (n = 86) recipients (1.42 ± 0.65 vs. 1.12 ± 0.66, p = 0.03). Ischemic kidneys with GG showed higher LIMS1 and GCC2 mRNA expression than kidneys with AG. Kidneys with rs893403-GG had higher tubular LIMS1 and GCC2 immunohistochemical staining compared to kidneys with rs893403-AG. CONCLUSIONS: Our data supports the role of the LIMS1 locus in kidney transplant rejection, particularly in lymphocyte infiltration into the internal aspect of the tubular basement membranes. Increased LIMS1 and GCC2 expression in ischemic donor kidneys with the GG genotype require further studies.

Clinical and histopathological characteristics of primary focal segmental glomerulosclerosis in Turkish adults.

The data regarding primary FSGS (pFSGS) from different parts of the world differ. While the prevalence of pFSGS has been increasing in Western countries like the USA, it follows an inconsistent trend in Europe and Asia and a decreasing trend in Far Eastern countries such as China in the last two decades. There are undetermined factors to explain those national and geographic discrepancies. Herein, we aimed to reveal the current prevalence with clinical and histopathological characteristics of pFSGS in Turkish adults. This study includes the biopsy-proven pFSGS patients data recorded between 2009 and 2019, obtained from the national multicenter primary glomerulonephritis registry system of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database. 850 of the 3875 primer glomerulonephritis patients(21.9%) have pFSGS. The mean age is 40.5 ± 14.2 and 435 (51.2%) of patients are male. Nephrotic syndrome is the most common biopsy indication (59.2%). 32.6% of patients have hematuria, 15.2% have leukocyturia and 7.8% have both. Serum creatinine, albumin, and proteinuria are 1.0 mg/dL (IQR = 0.7-1.4) mg/dl, 3.4 ± 0.9 g/dl, 3400 mg/day(IQR, 1774-5740), respectively. Females have lower mean arterial pressure (- 2.2 mmHg), higher eGFR (+ 10.0 mL/min/1.73 m2), and BMI (+ 1.6 kg/m2) than males. Thickened basal membrane(76.6%) and mesangial proliferation (53.5%) on light microscopy are the major findings after segmental sclerosis. IgM (32.7%) and C3 (32.9%) depositions are the most common findings on immunofluorescence microscopy. IgM positivity is related to lower eGFR, serum albumin, and higher proteinuria. The prevalence of pFSGS is stable although slightly increasing in Turkish adults. The characteristics of the patients are similar to those seen in Western countries.

Temporary hypothyroidism in severe crush syndrome: a potential novel entity.

BACKGROUND: Thyroid hormone synthesis is a complex process in the human body. Although the thyroid gland is essential for thyroid hormone synthesis, skeletal muscles also have crucial roles in thyroid hormone metabolism due to the deiodinase activities of the muscle cells. Hypothyroidism-related myopathy is a well-known entity. However, systemic effects of acute myopathies, such as rhabdomyolysis, on thyroid hormone metabolism have not to date been fully clarified. METHODS: Fifty-three earthquake victims were evaluated retrospectively. We investigated the thyroid function tests (TFTs) among patients with creatine kinase (CK) levels higher than 10.000 U/L at admission. Fifteen patients had CK levels higher than 10.000 U/L and 12 of them had data of TFTs, including thyroid stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) during hospitalization. These patients were evaluated. RESULTS: TSH levels were increased in all seven patients who required HD due to severe crush syndrome. Decreased FT4 levels were detected in 71.4% of them. None of the five non-HD patients had increased TSH levels or reduced FT4 levels. During follow-up, all patients survived. Renal and thyroid functions were normalized during follow-up without thyroxin replacement in patients with no prior history of hypothyroidism. Moreover, TFTs were normalized in two patients with history of hypothyroidism under thyroxine treatment without dose adjustments. CONCLUSIONS: In severe forms of crush syndrome, temporary hypothyroidism might be seen. The exact mechanism underlying this entity is not well-known. Further clinical and experimental trials should be conducted to illuminate the mechanism of disrupted thyroid hormonogenesis in crush syndrome victims.

Spatial Distribution of Macrophage Subtypes Among Rejection Subtypes in Renal Transplant Biopsies by Dual Immunohistochemistry.

We performed dual immunohistochemistry for CD163/CD34 and CD68/CD34 in 108 renal transplant indication biopsies to investigate the presence and distribution of macrophages in various renal compartments. All Banff scores and diagnoses were revised according to the Banff 2019 classification. CD163 and CD68 positive cell counts (CD163pos and CD68pos) were evaluated in the interstitium, glomerular mesangium, and, within glomerular and peritubular capillaries. The diagnosis was antibody-mediated rejection (ABMR) in 38 (35.2%), T-cell mediated rejection (TCMR) in 24 (22.2%), mixed rejection in 30 (27.8%), and no rejection in 16 (14.8%). Banff lesion scores t , i , and ti were correlated with both CD163 and CD68 interstitial inflammation scores ( r > 0.30; P < 0.05). Glomerular total CD163pos was correlated to Banff lesion scores g and cg ( r > 0.30; P < 0.05). Glomerular total, mesangial, and intracapillary CD68pos were correlated with g ( r > 0.30; P < 0.05). Both glomerular total and peritubular capillary CD68pos were correlated with peritubular capillaritis ( r > 0.30; P < 0.05). Glomerular CD163pos were significantly higher in ABMR compared with no rejection, in mixed rejection compared with no rejection and TCMR. CD163pos in peritubular capillaries was significantly higher in mixed rejection compared with no rejection. Glomerular CD68pos was significantly higher in ABMR compared with no rejection. CD68pos per peritubular capillary was higher in mixed rejection, ABMR, and TCMR compared with no rejection. In conclusion, compared with CD68 positive macrophages, localization of CD163 positive macrophages in various renal compartments seems to be different among rejection subtypes and their glomerular infiltration seems to be more specific for the presence of ABMR component.

Heme oxygenase-1 deficiency as an extremely rare cause of AA-type renal amyloidosis: Expanding the clinical features and review of the literature.

Heme oxygenase-1 (HMOX-1) is an enzyme that regulates heme degradation. Antiinflammatory, antioxidant, and cytoprotective effects of HMOX-1 were also described. It is encoded by the HMOX1 gene, and biallelic mutations cause HMOX-1 deficiency, which is a rare chronic multisystemic inflammatory disorder. This inflammatory status could lead to the development of secondary AA-type amyloidosis theoretically. Here, we report a 30-year-old male with AA-type renal amyloidosis due to a chronic inflammatory condition of unknown origin. Paternal consanguinity and dysmorphic features raised suspicion of a rare genetic disorder. Clinical exome sequencing (CES) confirmed the HMOX-1 deficiency diagnosis related to homozygous missense G139V mutation. To the best of our knowledge, our patient is the eleventh HMOX-1 deficiency case in the literature. Also, HMOX-1 deficiency-related systemic AA-type amyloidosis has not been reported before.

Long-term Effects of Gastric Acid Prophylaxis in Kidney Transplant Recipients.

Objectives: Prophylactic acid suppression with proton pump inhibitors or H2 receptor antagonists is often administered after kidney transplantation. The Association of proton pump inhibitors or H2 receptor antagonists with acute rejection, hypomagnesemia, and graft loss in kidney transplant recipients is not well established. Material and Methods: We performed a retrospective cohort study of 302 kidney transplant recipients at one center (57% male; mean age 35.5±11.2 years) with more than 6 months post-transplant follow-up. Recipients were grouped according to gastric acid prophylaxis: only proton pump inhibitors (n=179), only H2 receptor antagonists (n=42), proton pump inhibitors and H2 receptor antagonists (n=55), and nonusers (n=26). The primary outcome was biopsy-proven acute rejection. Graft loss and hypomagnesemia were defined as secondary outcomes. Results: Nonusers were younger and mostly under steroid-free immunosuppression compared to other study groups (p=0.030 and p=0.009, respectively). The primary outcome was similar across study groups (p=0.266). Kaplan-Meier analyses also demonstrated similar 10-year graft survival rates: 95.5% for proton pump inhibitors, 97.6% for H2 receptor antagonists, 100% for proton pump inhibitors/H2 receptor antagonists, and 96.2% for nonusers (p=0.275). Conclusions: The use of proton pump inhibitors is not associated with acute rejection or graft loss but may cause mild hypomagnesemia in kidney transplant recipients.

Diagnostic yield and safety of percutaneous native kidney biopsy in pregnancy: 20-years of single-center experience.

BACKGROUND: Percutaneous kidney biopsy is a fundamental procedure in nephrology. Although pregnancy is not a contraindication, a careful risk-benefit assessment is mandatory in pregnancy. We aimed to evaluate safety and diagnostic accuracy of percutaneous kidney biopsy in pregnancy in a single-center retrospective study. METHODS: Percutaneous kidney biopsy was performed in 19 pregnant patients. Demographics, estimated glomerular filtration rates, serum albumin levels, and proteinuria levels at the time of biopsy were evaluated. Biopsy-related complications, diagnoses, and treatments during the follow-up were analyzed. In addition, delivery success, preeclampsia, early delivery, low birth weight rates, and long-term outcomes of the patients were retrieved and analyzed. RESULTS: Mean patient age was 27 (range 16-41) years. Median gestational week at kidney biopsy was 20th. All but one biopsies were diagnostic. Median gestational week of delivery was 35 (range 23-39) gestational weeks. Preterm delivery (< 37 gestational weeks) and low birth weight (< 2500 mg) occurred in 73.7% and 52.6% of cases, respectively. Median weight at birth was 2500 mg. The incidence of preeclampsia was 57.9%. Overall 89.5% of the children survived. Median post-biopsy follow-up was 64 months. Maternal mortality was not observed during the follow-up period. End stage kidney disease developed in one patient. The results of percutaneous kidney biopsy led to therapeutic decisions in 73.7% of cases. CONCLUSIONS: Although percutaneous kidney biopsy is not frequently performed during pregnancy, it is relatively safe and usually diagnostic, and may guide further follow-up.