Causes of Granulomatous Inflammation in Native and Allograft Kidneys: Case Series from A Single Center and A Review of the Literature.

OBJECTIVE: Granulomatous interstitial nephritis is a rare finding, and etiology differs by geography. We aimed to investigate the distribution of causes of granuloma/granulomata in the kidney and renal survival of these patients in a tertiary care hospital in Western Turkey. MATERIAL AND METHOD: Medical records of adults who underwent a kidney biopsy procedure in our institution between January 2000 and June 2019 were reviewed. Pathology reports were searched for biopsies where a granuloma was identified. RESULTS: Nineteen of 1121 (1.7%) kidney biopsies included granuloma, 17 in native kidneys, and 2 in transplants. The majority of indications for native kidney biopsy was a rise in serum creatinine. Etiologies of granuloma included the following: pauci-immune vasculitis (n=11, 64.7%), tuberculosis (n=2, 11.8%), drug-induced (n=2, 11.8%), tubulointerstitial nephritis/uveitis (TINU) syndrome (n=1, 5.9%), and systemic-lupus erythematosus (n=1, 5.9%). Despite treatment, 6 of 11 (54.5%) patients with vasculitis developed end-stage kidney disease (ESKD) during the median follow-up of 16 months. Both of the patients with tuberculosis, and the patient with TINU syndrome developed ESKD months after the kidney biopsy, despite appropriate therapies. The only case with drug-induced granuloma and both cases with allograft kidney granuloma responded well to glucocorticoids, achieving a complete renal recovery. CONCLUSION: The majority of our series had granuloma in the kidney secondary to vasculitis and renal outcomes appear considerably unfavorable despite treatment, probably related to the primary diagnosis. Multicenter studies are needed to better determine the etiology and outcome of each granuloma etiology at different geographic locations.

Acute kidney injury following colistin treatment in critically-ill patients: may glucocorticoids protect?

Nephrotoxicity following colistin administration is common and factors alleviating nephrotoxicity are yet to be determined. We retrospectively evaluated outcomes of subjects who were treated with colistin (n = 133) and with antibiotics other than colistin (control, n = 133) in intensive care units. Acute kidney injury (AKI) occurred in 69.2% and 29.3% of patients in colistin and control groups, respectively (p < 0.001). In the colistin group, glucocorticoid exposure was more common in subjects who did not develop AKI (p < 0.001). This was not the case in the control group. In the colistin cohort, older age (per 10 years, odds ratio [OR] 1.41, 95% CI 1.05-1.91; p = 0.025), PPI use (OR 3.30, 95% CI 1.18-9.23; p = 0.023) and furosemide treatment (OR 2.66, 95% CI 1.01-6.98; p = 0.047) were independently associated with the development of AKI while glucocorticoid treatment (OR 0.23, 95% CI 0.10-0.53; p = 0.001) was independently associated with reduced risk of AKI. Mortality was observed in 74 patients in the colistin cohort (55.6%). A higher APACHE-II score (OR 1.17, 95% CI 1.08-1.26; p < 0.001) was independently associated with mortality while a higher serum albumin level (per 1 g/dL increase, OR 0.20, 95% CI 0.070-0.60; p = 0.004) was associated with a lower risk of mortality. In conclusion, glucocorticoid exposure is associated with a lower risk of AKI caused by colistin therapy in critically-ill patients. Prospective studies are needed to confirm these findings and determine the optimal type, dose and duration of glucocorticoid therapy.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma.

AIMS: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. SUBJECTS AND METHODS: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. RESULTS: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. CONCLUSIONS: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies.

Renal tubular P-glycoprotein expression is reduced in plasma cell disorders.

BACKGROUND: P-glycoprotein (P-gp) transports many chemicals that vary greatly in their structure and function. It is normally expressed in renal proximal tubular cells. We hypothesized that P-gp expression influences light chain excretion. Therefore, we investigated whether renal tubular P-gp expression is altered in patients with plasma cell disorders. METHODS: We evaluated renal biopsy specimens from patients with plasma cell disorders (n = 16) and primary focal segmental glomerulosclerosis (the control group, n = 17). Biopsies were stained with an anti-P-gp antibody. Loss of P-gp expression was determined semi-quantitatively. Groups were compared for loss of P-gp expression, and clinical variables. RESULTS: P-gp expression loss was more severe in patients with plasma cell disorders than it was in those with glomerulonephritis (P = 0.021). In contrast, clinical and histological parameters including serum creatinine, level of urinary protein excretion, and interstitial fibrosis/tubular atrophy grade were not significantly different between the groups. P-gp expression loss increased with age in patients with plasma cell disorders (P = 0.071). This expression loss was not associated with serum creatinine, the level of urinary protein excretion or the interstitial fibrosis/tubular atrophy grade. There was no significant association between the severity of P-gp expression loss with the types and serum levels of light chains, isotypes and serum immunoglobulin levels. CONCLUSION: Renal tubular P-gp expression is significantly down-regulated in patients with plasma cell disorders characterized by nephrotic range proteinuria. Additional studies are needed to determine whether reintroduction of renal tubular P-gp expression would mitigate the proximal tubular injury that is caused by free-light chains.

Clinical significance of mesangial IgM deposition in patients with IgA nephropathy.

BACKGROUND: Glomerular immunoglobulin G deposition in patients with immunoglobulin A nephropathy (IgAN) has been shown to be associated with adverse renal outcomes. Clinical significance of mesangial immunoglobulin M (IgM) deposition in these patients remains to be proven. METHODS: One hundred patients who had a diagnosis of IgAN between 2001 and 2017 were enrolled. Patients were divided into two groups based on mesangial IgM deposition status. Groups were compared for demographic, clinical, and pathologic variables at baseline and in follow-up. Cox regression analysis was performed to evaluate the effect of mesangial IgM positivity on renal survival. RESULTS: IgM-positive group included 51% of participants. Baseline demographic and clinical parameters were not significantly different between groups. Mesangial IgM deposition was significantly associated with a higher segmental sclerosis score (p = 0.008). At last visit, median serum creatinine was higher (p = 0.021) and eGFR was lower (p = 0.006) in IgM-positive group. Nineteen (19%) of all patients reached the combined primary outcome which includes doubling in serum creatinine or evolution to ESRD. Cumulative renal survival was lower (p = 0.001) and resistant disease was more frequent in IgM-positive group (p = 0.026). Renal survival at 15 years was 94.2% and 59.7% in IgM-negative and IgM-positive groups, respectively (p = 0.006). Time-averaged proteinuria (HR 2.9; 95% CI 1.9-4.5; p < 0.001) and mesangial IgM deposition (HR, 13.2; 95% CI 1.9-93.1; p = 0.01) were found to be independent predictors of unfavorable renal outcomes. CONCLUSIONS: In conclusion, we demonstrated that mesangial IgM deposition independently associated with worse renal outcomes in patients with IgA nephropathy.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma.

AIMS: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. SUBJECTS AND METHODS: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. RESULTS: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. CONCLUSIONS: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies.

Correlation Between Baseline 18F-FDG PET/CT Findings and CD38- and CD138-Expressing Myeloma Cells in Bone Marrow and Clinical Parameters in Patients with Multiple Myeloma

Objective: The aim of this study was to evaluate the relation between the rate of fluorine-18 (18F) fludeoxyglucose (FDG) uptake and CD38 and CD138 expression in myeloma cells in bone marrow and other clinical parameters in patients with multiple myeloma (MM). Materials and Methods: Patients with the diagnosis of MM who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) for initial staging were evaluated retrospectively. We analyzed a total of 42 patients (43-83 years old, mean: 64.4±9.9). Hematological and biochemical tests including hemoglobin, hematocrit, C-reactive protein, ß2-microglobulin, creatinine, albumin, calcium, lactate dehydrogenase, and erythrocyte sedimentation rate were recorded. In bone marrow samples, plasma cell ratio and CD38 and CD138 immunohistochemical staining were evaluated. On PET/CT images, mean standardized uptake values (SUVmean) of the right anterior and posterior iliac crest and right proximal femora were calculated. The correlations between the average SUVmean of bone marrow and CD38- and CD138-expressing myeloma cells and other parameters were analyzed by Spearman's correlation test. Values of p<0.05 were considered statistically significant. Results: Types of MM were IgGK (45%), IgGL (21%), IgAK (7%), IgAL (10%), and others (17%). Thirty-two (76%) patients were at stage III according to the Salmon-Durie staging system. There was a statistically significant positive correlation between bone marrow FDG uptake and percentage of plasma cells in bone marrow and CD38 and CD138 expression in plasma cells (r=0.403, r=0.339, and r=0.409) and ß2-microglobulin and C-reactive protein levels (r=0.676, r=0.541). There was a negative correlation between bone marrow FDG uptake and hemoglobin and hematocrit values (r=-0.377 and r=-0.368). Other hematological parameters were not correlated with FDG uptake in bone marrow. Conclusion: Increased FDG uptake is correlated with the percentage of CD38 and CD138 expression in plasma cells in bone marrow. In addition to initial staging, 18F-FDG PET/CT is useful in treatment planning and prognostic evaluation in MM patients.