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.

A case of Alport syndrome with pregnancy-related atypical hemolytic uremic syndrome and crescentic glomerulonephritis.

Kidney function may be impaired during pregnancy due to various reasons, and the physiological changes of pregnancy may unmask or worsen pre-existing kidney disease. Herein, we report a pregnant patient presenting with nephrotic-range proteinuria. She later developed acute kidney injury and pre-eclampsia. However, hemolytic anemia and thrombocytopenia persisted after delivery, and she was diagnosed with atypical hemolytic uremic syndrome (aHUS). Although hematological abnormalities resolved with eculizumab treatment, her renal functions did not improve. Kidney biopsy showed crescentic glomerulonephritis without thrombotic microangiopathy features. Concurrently, she was evaluated for hearing impairment, and a diagnosis of Alport syndrome was confirmed with genetic testing. Kidney function may worsen in patients with Alport syndrome during pregnancy. However, crescentic glomerulonephritis (GN) is a rare finding in Alport disease. Pauci-immune crescentic GN has been shown to be related to dysregulated activation of the alternative complement pathway, which is also the underlying pathophysiological mechanism in aHUS.

Propensity score-matched analysis of long-term outcomes for living kidney donation in alternative complement pathway diseases: a pilot study.

BACKGROUND: Atypical hemolytic syndrome (aHUS) and C3 glomerulopathy (C3G) are complement-mediated rare diseases with excessive activation of the alternative pathway. Data to guide the evaluation of living-donor candidates for aHUS and C3G are very limited. The outcomes of living donors to recipients with aHUS and C3G (Complement disease-living donor group) were compared with a control group to improve our understanding of the clinical course and outcomes of living donation in this context. METHODS: Complement disease-living donor group [n = 28; aHUS(53.6%), C3G(46.4%)] and propensity score-matched control-living donor group (n = 28) were retrospectively identified from 4 centers (2003-2021) and followed for major cardiac events (MACE), de novo hypertension, thrombotic microangiopathy (TMA), cancer, death, estimated glomerular filtration rate (eGFR) and proteinuria after donation. RESULTS: None of the donors for recipients with complement-related kidney diseases experienced MACE or TMA whereas two donors in the control group developed MACE (7.1%) after 8 (IQR, 2.6-12.8) years (p = 0.15). New-onset hypertension was similar between complement disease and control donor groups (21.4% vs 25%, respectively, p = 0.75). There were no differences between study groups regarding last eGFR and proteinuria levels (p = 0.11 and p = 0.70, respectively). One related donor for a recipient with complement-related kidney disease developed gastric cancer and another related donor developed a brain tumor and died in the 4th year after donation (2, 7.1% vs none, p = 0.15). No recipient had donor-specific human leukocyte antigen antibodies at the time of transplantation. Median follow-up period of transplant recipients was 5 years (IQR, 3-7). Eleven (39.3%) recipients [aHUS (n = 3) and C3G (n = 8)] lost their allografts during the follow-up period. Causes of allograft loss were chronic antibody-mediated rejection in 6 recipients and recurrence of C3G in 5. Last serum creatinine and last eGFR of the remaining patients on follow up were 1.03 ± 038 mg/dL and 73.2 ± 19.9 m/min/1.73 m2 for aHUS patients and 1.30 ± 0.23 mg/dL and 56.4 ± 5.5 m/min/1.73 m2 for C3G patients. CONCLUSION: The present study highlights the importance and complexity of living related-donor kidney transplant for patients with complement-related kidney disorders and motivates the need for further research to determine the optimal risk-assessment for living donor candidates to recipients with aHUS and C3G.

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.

Fibroscan detection of fatty liver and liver fibrosis in patients with systemic lupus erythematosus.

OBJECTIVE: Although liver dysfunction is not considered the main organ involvement in Systemic Lupus Erythematosus (SLE), the frequency of liver dysfunction or abnormal liver enzyme values may be observed in 50-60% of patients. The aim of this study was to assess fatty liver and liver fibrosis in SLE patients using Fibroscan as well as determine associated factors such as immunosuppressive medications. METHODS: Sixty SLE patients and 30 healthy controls were included. Patients with HBV, HCV or cirrhosis, malignancy, cardiac disease, or patients on dialysis were excluded. All participants underwent Fibroscan measurements. RESULTS: The prevalence of fatty liver disease was similar between SLE patients and healthy controls (21.7 vs 26.7%, p = .597). Liver fibrosis was also similar between the two groups (26.7 vs 10.0%, p = .069). Since the majority of SLE patients were female, we performed a subgroup analysis in female patients (n = 51) and controls (n = 25). Fatty liver disease was similar between female SLE patients and controls (23.5 vs 24.0%, p = .964). However, liver fibrosis in female patients with SLE was increased compared to female controls (29.4 vs 4.0%, p = .011) and was associated with age (Exp (B) 95% CI: 1.083 (1.006-1.166), p = .034) and low-dose cumulative glucocorticoid use (Exp (B) 95% CI: 14.116 (1.213-164.210), p = .034). CONCLUSION: The prevalence of fatty liver was similar between SLE patients and controls, while liver fibrosis was increased in the female patient group as compared to controls. Furthermore, liver fibrosis was associated with age and low dose cumulative glucocorticoid use. Interestingly, fatty liver did not precede liver fibrosis in the majority of cases, contrary to what is observed in the general population. Larger studies are needed to confirm our findings and determine whether immunosuppressive use has any impact on the development of liver fibrosis in SLE patients.

Assessment of peritoneal thickness using CT in relation to dialysis adequacy in peritoneal dialysis patients.

Studies assessing peritoneal thickness by CT in peritoneal dialysis (PD) patients are lacking. In this study, we aimed to investigate the association between peritoneal thickness as measured by CT and dialysis adequacy with peritoneal membrane characteristics in PD patients. Ninety-four PD patients were enrolled. Peritoneal thickness was measured by CT. Patients with and without a decrease in Kt/V of at least 0.3 over time were classified as Group 1 and Group 2, respectively. An increase of 0.1 unit of dialysate/plasma (D/P) creatinine over time were considered significant. The relationship between peritoneal membrane thickness, change in Kt/V, and peritoneal membrane characteristics were investigated. There were 31 (33.0%) patients in Group 1. The duration of PD (86.0 ± 64.1 vs. 59.6 ± 45.2 months, p: 0.023), peritoneal thickness (1.02 ± 0.37 vs. 0.87 ± 0.21 mm, p: 0.015), peritoneal calcification (7 [22.6%] vs. 3 [4.8%] patients, p: 0.013], increased D/P creatinine ratio (14 [45.2%] vs. 14 [22.2%] patients, p: 0.031) and CRP (13.9 ± 11.2 vs. 7.1 ± 4.8 mg/L, p: 0.045) were significantly higher in Group 1, whereas albumin (3.6 ± 0.5 vs. 3.8 ± 0.6 g/dL, p: 0.047) and parathyroid hormone (355.2 ± 260.2 vs. 532.1 ± 332.9 ng/L, p: 0.015) levels were significantly lower. Peritoneal thickness was significantly correlated with duration of PD (r: 0.775, p < 0.001) and CRP (r: 0.282, p: 0.006). Regression analysis showed that peritoneal thickness (Exp (B) [95% CI]: 0.029 [0.003-0.253], p: 0.001) was independent predictor of decreased Kt/V in PD patients. In conclusion, prolonged PD duration and increased peritoneal thickness are associated with a decrease in Kt/V over time. CT may be an alternative and noninvasive method instead of peritoneal biopsy for determining the structural changes of the peritoneal membrane .

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.

The prevalence of metabolic syndrome is increased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

PURPOSE: Cardiovascular disease is one of the major causes of mortality in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Metabolic syndrome (MetS) is associated with increased cardiovascular risk in the normal population. However, MetS in AAV has not been adequately investigated. We aimed to determine MetS prevalence and associated factors in AAV patients. METHODS: Thirty-seven AAV patients and 42 healthy controls were enrolled. MetS was determined by International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria. The relationship between clinical features of AAV and MetS was also investigated. RESULTS: MetS was significantly higher in AAV patients than controls by NCEP-ATPIII (51.4% vs. 26.2%, p 0.022) and IDF (62.2% vs. 35.7%, p 0.020). When AAV patients with MetS were compared to those without, there were significant differences in age, CRP, GFR and NT-pro-BNP. Age [58 (13) vs. 50 (8) years p: 0.028], CRP [4.0 (3.6) vs. 3.2 (1.0) mg/l, p 0.021] and NT-pro-BNP [173.5 (343.7) vs. 106.0 (103.0) pg/ml, p 0.013] were significantly higher in AAV patients with MetS than those without; GFR was significantly lower [38 (46) vs. 83 (51) ml/min/1.73 m2, p 0.004]. ROC curve analysis showed NT-pro-BNP > 58.0 ng/ml predicted MetS with 87.1% sensitivity and 46.7% specificity (Area under curve: 0.71, CI 0.536-0.902, p 0.041). Multivariate analysis revealed age [OR (95% CI): 1.180 (1.010-1.370), p 0.039] and NT-pro-BNP > 58 pg/ml [OR (95% CI): 5.5 (1.02-30.1) p 0.047] were independent predictors of MetS in AAV patients. CONCLUSION: MetS is significantly higher in AAV patients than controls and is associated with age and NT-pro-BNP. Screening and treating MetS may improve prognosis in AAV patients.

Role of diffusion-weighted MR imaging in the differentiation of benign retroperitoneal fibrosis from malignant neoplasm: preliminary study.

PURPOSE: To evaluate diffusion-weighted imaging (DWI) features and signal intensity values at T2-weighted magnetic resonance (MR) imaging for differential diagnosis of benign retroperitoneal fibrosis (RPF) and plaque-like retroperitoneal malignant neoplasms. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this retrospective study. Fifty-one patients with plaque-like confluent retroperitoneal soft-tissue masses were divided into three groups: group I, 25 patients with malignant RPF and retroperitoneal malignant neoplasm; group II, 16 patients with chronic RPF; and group III, 10 patients with active RPF. On T1-weighted (unenhanced and contrast material-enhanced), T2-weighted, and DWI (b = 1000 sec/mm(2)) images, apparent diffusion coefficient (ADC) values and quotients of postcontrast signal intensities between lesions and psoas muscle were evaluated. The χ(2) test was used to compare categorical values; one-way analysis of variance and Kruskal-Wallis tests were used to compare groups. RESULTS: Overall sensitivity, specificity, and positive and negative predictive values of DWI findings were 92% (23 of 25 patients), 62% (16 of 26 patients), 70% (23 of 33 patients), and 89% (16 of 18 patients), respectively. Mean ADC values were 0.79 ± 0.19 in group I, 1.43 ± 0.16 in group II, and 0.91 ± 0.14 in group III. When comparing values, differences between groups I and II (ADC values, P < .0001; DWI quotients, P < .0001; postcontrast quotients, P = .001) and groups II and III (ADC values, P < .0001; DWI quotients, P = .016; postcontrast quotients, P = .04) were significant. There was no significant difference between groups I and III or between the three groups when T2-weighted values were compared. CONCLUSION: ADC of chronic RPF was higher than that for active RPF or malignant RPF and retroperitoneal malignant neoplasm. DWI can contribute to differential diagnosis of chronic RPF and malignant neoplasms with RPF morphology. Lesions in the malignant group and active RPF group had similar enhancement patterns, while those in the chronic RPF group demonstrated less enhancement. Signal intensity values on T2-weighted images were not useful for differentiating these conditions.

Determinants of hemoglobin variability in stable peritoneal dialysis patients.

PURPOSE: Significant within-patient hemoglobin (Hb) level variability is well recognized in particularly hemodialysis patients. Several factors such as hospitalizations, intercurrent diseases and IV iron therapy are found to be related to Hb variability (Hb-var). In this observational study, we aimed to identify predictors and outcome of Hb-var in peritoneal dialysis (PD) patients without hospitalization, intercurrent disease and IV iron therapy during the study period. METHODS: All patients were in the maintenance phase of short-acting erythropoiesis-stimulating agents (ESAs) therapy. The target range of Hb was 11-12 g/dL according to KDOQI Guidelines in 2007. The desired range of Hb was 11-12.5 g/dL. Patients' demographic and laboratory data were collected at baseline. Atherosclerotic disease was assessed using carotid intima-media thickness (CIMT). We assessed Hb variability with various methods using SD Hbmean, SD Hbrange and the velocity of Hb change. Hb deflectpositive, Hb deflectnegative, Hb values and ESA dosing were recorded monthly for 6 months. RESULTS: This study included 50 prevalent PD patients (mean age 46.9 ± 13.7 years, 25 women). The mean velocity of Hb change was negatively correlated with age and positively correlated with frequent ESA dose changes. Higher albumin and residual renal function (RRF) were also positively correlated with Hb deflectpositive. Patients with CIMT ≥0.7 cm had lower SD Hb range compared to CIMT <0.7 cm. Cumulative survival was better in patients with Hb levels consistently ≥10 g/dL compared to patients who had Hb <10 g/dL for at least 1 month. However, Hb-var was not associated with mortality. CONCLUSIONS: In PD patients without hospitalization, intercurrent disease(s) or IV iron therapy, young age, higher albumin or RRF and lower CIMT were associated with greater oscillations in response to ESA therapy. Careful and appropriate ESA dose changes considering these parameters could minimize Hb variability in these patients.