Effect of antimalarials on clinical outcomes in lupus nephritis.

OBJECTIVES: To evaluate the effect of antimalarial drugs in response to therapy, incidence of LN flares, and progression of kidney disease in a large LN cohort. METHODS: We retrospectively studied 424 biopsy-proven LN patients followed for >3 years. We obtained demographic, clinical, laboratory, histopathological, and treatment variables. Antimalarial use was approached as 1) users versus no users, 2) according to prevalent vs incident use regarding the LN flare, and 3) according to the type of antimalarial. All outcomes were evaluated by time-to-event analyses. Adjusted hazard ratios were obtained by Cox regression. RESULTS: The cohort included 424 patients, median age of 29 years (IQR 23-37), 96% female, with a median eGFR of 81 ml/min/1.73m2 (IQR 48-118) and proteinuria of 3.4 g/g (IQR 1.9-5.5). Antimalarial use was associated with higher complete response (aHR 1.57, 1.08-2.27), lower incidence of kidney flares (aHR 0.63, 0.43-0.92), and lower progression to kidney failure (aHR 0.37, 0.23-0.53). The effect on these outcomes was modified by the presentation eGFR, histological class, and/or concomitant initial immunosuppressor. These protective effects were observed in patients with prevalent or incident use regarding the LN flare and patients using hydroxychloroquine. The incidence of toxic retinopathy was 1.7%, 5.7%, and 8.8% by 3-, 5-, and 7 years of continued antimalarial use. CONCLUSION: The use of antimalarial drugs is associated with increased response to therapy, lower incidence of kidney flares, and lower progression to kidney failure in LN patients. Conversely, this population is at high risk of toxic maculopathy, and yearly ophthalmologic examination is recommended.

Effect of Kidney transplantation on cyst growth in autosomal dominant polycystic kidney disease.

BACKGROUND: In patients with autosomal dominant polycystic kidney disease (ADPKD), there is limited evidence of the rate of cyst progression after kidney transplantation. AIMS: To compare the height-adjusted total kidney volume (Ht-TKV) before and after transplantation in kidney transplant recipients (KTR) with -ADPKD. MATERIALS AND METHODS: Retrospective cohort study. The estimate of Ht-TKV was calculated by the ellipsoid volume equation using measurements from CT or yearly MRI scans before and after transplantation. RESULTS: We included 30 patients with -ADPKD who underwent kidney transplantation (age 49 ± 10.1 years, 11 (37%) females, dialysis vintage 3 (1 - 6) years, and 4 (13%) underwent unilateral nephrectomy during the peritransplant period). The median follow-up time was 5 years (range 2 - 16 years). Transplantation was associated with a significant decrease in Ht-TKV after transplantation in 27 (90%) KTR. Median Ht-TKV decreased from 1,708 (IQR 1,100 - 2,350) mL/m to 710 (IQR 420 - 1,380) mL/m after 6 years of follow-up (p < 0.001), with a mean Ht-TKV change rate per year after transplantation of -1.4, -11.8, -9.7, -12.7, -7.0, and -9.4% after 1, 2, 3, 4, 5, and 6 years, respectively. Even in 2 (7%) KTR without regression, the annual growth was < 1.5% per year after transplantation. CONCLUSION: Kidney transplantation reduced Ht-TKV after the first 2 years of transplantation, and this decline was continuous for more than 6 years of follow-up.

Highly purified and functionally stable in vitro expanded allospecific Tr1 cells expressing immunosuppressive graft-homing receptors as new candidates for cell therapy in solid organ transplantation.

The development of new strategies based on the use of Tr1 cells has taken relevance to induce long-term tolerance, especially in the context of allogeneic stem cell transplantation. Although Tr1 cells are currently identified by the co-expression of CD49b and LAG-3 and high production of interleukin 10 (IL-10), recent studies have shown the need for a more exhaustive characterization, including co-inhibitory and chemokines receptors expression, to ensure bona fide Tr1 cells to be used as cell therapy in solid organ transplantation. Moreover, the proinflammatory environment induced by the allograft could affect the suppressive function of Treg cells, therefore stability of Tr1 cells needs to be further investigated. Here, we establish a new protocol that allows long-term in vitro expansion of highly purified expanded allospecific Tr1 (Exp-allo Tr1). Our expanded Tr1 cell population becomes highly enriched in IL-10 producers (> 90%) and maintains high expression of CD49b and LAG-3, as well as the co-inhibitory receptors PD-1, CTLA-4, TIM-3, TIGIT and CD39. Most importantly, high dimensional analysis of Exp-allo Tr1 demonstrated a specific expression profile that distinguishes them from activated conventional T cells (T conv), showing overexpression of IL-10, CD39, CTLA-4 and LAG-3. On the other hand, Exp-allo Tr1 expressed a chemokine receptor profile relevant for allograft homing and tolerance induction including CCR2, CCR4, CCR5 and CXCR3, but lower levels of CCR7. Interestingly, Exp-allo Tr1 efficiently suppressed allospecific but not third-party T cell responses even after being expanded in the presence of proinflammatory cytokines for two extra weeks, supporting their functional stability. In summary, we demonstrate for the first time that highly purified allospecific Tr1 (Allo Tr1) cells can be efficiently expanded maintaining a stable phenotype and suppressive function with homing potential to the allograft, so they may be considered as promising therapeutic tools for solid organ transplantation.

Characteristics and outcomes of a Hispanic lupus nephritis cohort from Mexico.

OBJECTIVES: To characterize the clinical presentation and outcomes of LN in a Hispanic cohort from Mexico. METHODS: We studied 440 subjects with systemic lupus erythematosus and biopsy-proven LN followed for >36 months. We obtained demographic, clinical, laboratory, histopathological and treatment variables. All outcomes were analysed by survival analysis and included response to therapy, renal relapses, progression of kidney disease (decline in eGFR ≥ 30%, doubling of serum creatinine, end-stage kidney disease) and patient survival. RESULTS: The median age of the study cohort was 29 years (IQR 23-37) and 96% were female. The median eGFR at inclusion was 81 mL/min/1.73m2 (IQR 48-118) and 24 h-uPCR was 3.4 g/g (IQR 1.9-5.6). Mixed class LN (III/IV+V) was the most frequently observed (69%). Over a median follow-up of 79 months, complete response rates were 22.3%, 40.5% and 51.6%, at 6, 12 and 24 months, respectively. Renal relapse rates were 32.3% and 50.6% at 3 and 5 years. By 3 and 5 years, 20.7% and 31.4% had decline in eGFR ≥30%, 14.4% and 22.5% doubled their serum creatinine, and 9.1% and 17.7% progressed to ESKD. The factors associated with loss of kidney function were age, eGFR at presentation, the histologic chronicity index in the kidney biopsy, and the type of response to therapy. Patient survival was 98.2% and 97.1% at 3 and 5 years. CONCLUSION: Although the response to treatment and patient survival in this Latin American cohort is comparable to that observed in other regions, there is still a high rate of renal relapses and progression to decline in kidney function.

Leukocyte Chemotactic Factor 2 Amyloidosis (ALECT2) Distribution in a Mexican Population.

OBJECTIVES: To assess the prevalence of leukocyte cell-derived chemotactic 2 (LECT2), its organ involvement, and its clinical association in autopsies from an ethnically biased population. METHODS: The tissues from all autopsies of individuals diagnosed with amyloidosis were reassessed and typed for amyloid light chain (AL) amyloidosis, amyloid A (AA) amyloidosis, transthyretin amyloidosis (ATTR), and leukocyte chemotactic factor 2 amyloidosis (ALECT2) by immunohistochemistry. Organ involvement was described and correlated with its clinical associations. RESULTS: Of 782 autopsies, 27 (3.5%) had a confirmed diagnosis of amyloidosis. Of these, 14 (52%) corresponded to ALECT2, 5 (19%) to AL amyloidosis, 2 (7%) to ATTR amyloidosis, 1 (4%) to AA amyloidosis, and 5 (21%) as undetermined-type amyloidosis. The LECT2 amyloid deposits were found in the kidneys, liver, spleen, and adrenal glands in most individuals. Except for the kidneys, there were no clinical signs suggestive of amyloid deposition in most of the affected organs. LECT2 amyloidosis was not associated with the cause of death in any case. No cases had heart or brain involvement. Potential subclinical effects of amyloid deposition in organs such as adrenal glands and spleen require further study. CONCLUSIONS: This autopsy study confirms the high prevalence of LECT2 amyloidosis in the Mexican population, with frequent amyloid deposition in the kidneys, liver, spleen, and adrenal glands.

The influence of repeated flares in response to therapy and prognosis in lupus nephritis.

BACKGROUND: Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney and patient prognosis. METHODS: All patients from a biopsy-proven LN cohort between 2008 and 2018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the estimated glomerular filtration rate (eGFR), doubling of serum creatinine, end-stage kidney disease and patient survival. RESULTS: A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria and hematuria among groups. The National Institutes of Health chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups. CONCLUSIONS: A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival.

Sub-classification of borderline changes into diffuse or focal and its impact on long-term renal transplant outcomes.

BACKGROUND: Borderline changes (BL) with stable renal function is a controversial category in renal transplantation, given its contradictory outcomes. The aim of this study was to compare the clinical outcomes of BL in patients with stable renal function classified as focal and diffuse according to the extent of tubulitis. METHODS: Patients with no history of rejection with a surveillance graft biopsy at 3 or 12 months showing BL (n = 40), acute cellular rejection (n = 20) or normal biopsies (n = 20), were included in this study. Biopsies with BL were divided into diffuse BL (BLD) and focal BL (BLF) according to the extent of tubulitis. Because of the low frequency of subclinical ACR (ACRND) (n = 12), biopsies with ACR and graft dysfunction (ACRD) (n = 8) were also included. A composite outcome that included the presence of rejection in subsequent biopsies, graft loss, patient death, decrease in GFR ≥30% or presence of de novo DSA (dnDSA) during the first year of follow-up was evaluated. RESULTS: The primary composite outcome occurred in five patients of each of the Normal, BLF and ACRND, eight patients with BLD and six patients with ACRD (p = 0.105). A trend towards more rejection episodes was observed in the ACRND and ACRD. Also, a shorter time to rejection in the BLD, ACRND and ACRD groups compared to BLF and Normal groups (p = 0.039) was observed. During the first year of follow-up, no patient in the ACRND group developed dnDSA, compared to 15-25% in the other groups. The median time of dnDSA development in the BLF group was 45 months, and in the BLD group was 10 months (p = 0.020). CONCLUSION: Classifying BL biopsies with stable renal function into focal and diffuse categories, is a simple and feasible strategy that helps to differentiate between BLD with a phenotype that shows a trend towards worse outcomes, and BLF that behaves more similar to normal biopsies.

Acute kidney injury in critically ill patients after oncological surgery: Risk factors and 1-year mortality.

AIM: We aimed to identify risk factors associated with acute kidney injury (AKI) and to analyse 1-year mortality after oncological surgery. METHODS: We retrospectively included 434 adult patients admitted to the intensive care unit (ICU) after oncological surgery, and classified AKI according to the Kidney Disease: Improving Global Outcomes criteria. We performed logistic regression and Cox regression analyses to evaluate AKI and mortality risk factors. RESULTS: Sixty-one percent of patients (n = 264) developed AKI. Previous abdominal radiotherapy and abdominal surgical packing were independently associated with stage 2 and 3 AKI, with adjusted odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.3-5.5, p = .010) and OR of 2.6 (95% CI 1.2-5.5, p = .014), respectively. Other independent risk factors were: glomerular filtration rate (eGFR) <60 ml/min/1.73m2 (OR 3.6, 95% CI 1.2-11.4, p = .028), abdominal surgery 2.6 (1.4-4.9, p = .003), intraoperative diuresis <1 ml/k/h (OR 2.4, 95% CI 1.4-4.0, p = .001), sepsis (OR 2.5, 95% CI 1.3-4.6, p = .002) and mechanical ventilation at ICU admission (OR 7.7, 95% CI 3.2-18.6, p < .001). Stage 2 and stage 3 AKI were independently associated with 1-year mortality, with adjusted hazard ratios (HR) of 2.6 (95% CI 1.3-5.0, p = .005) and HR of 5.0 (95% CI 2.6-9.6, p < .001), respectively. Additionally, patients who had postsurgical AKI, had a lower eGFR at 1-year follow-up. These findings may be limited by the retrospective single centre design of our study. CONCLUSION: In addition to the conventional risk factors, our results suggest that abdominal radiotherapy and abdominal surgical packing could be independent risk factors for AKI after oncological surgery.

Fibroblast growth factor 21 is associated with increased serum total antioxidant capacity and oxidized lipoproteins in humans with different stages of chronic kidney disease.

Background and aims: Oxidative stress (OS) induces the production of fibroblast growth factor 21 (FGF21). Previous data have revealed that FGF21 protects cells from OS injury and death, making it a potential therapeutic option for many diseases with increased OS. However, the association of this growth factor with OS markers in humans with chronic kidney disease (CKD) remains unknown. This study aims to evaluate the association of serum FGF21 with serum total antioxidant capacity (TAC) and oxidized low-density lipoproteins (OxLDL) in subjects in different stages of kidney disease. Methods: This is a cross-sectional study that included 382 subjects with different stages of CKD, irrespective of type 2 diabetes (T2D) diagnosis. Associations of serum FGF21 with OxLDL, TAC, sex, age, body mass index (BMI), fasting plasma glucose, estimated glomerular filtration rate (eGFR), T2D, and smoking, were evaluated through bivariate and partial correlation analyses. Independent associations of these variables with serum FGF21 were evaluated using multiple linear regression analysis. Results: Serum FGF21 was significantly and positively correlated with age (r = 0.236), TAC (lnTAC) (r = 0.217), and negatively correlated with eGFR (r = -0.429) and male sex (r = -0.102). After controlling by age, sex, BMI, T2D, smoking, and eGFR; both TAC and OxLDL were positively correlated with FGF21 (r = 0.117 and 0.158 respectively, p < 0.05). Using multiple linear regression analysis, eGFR, male sex, T2D, OxLDL, and TAC were independently associated with serum FGF21 (STDß = -0.475, 0.162, -0.153, 0.142 and 0.136 respectively; p < 0.05 for all) adjusted for age, BMI, smoking, and fasting plasma glucose. Conclusion: A positive association between serum FGF21 and OS has been found independently of renal function in humans. Results from the present study provide novel information for deeper understanding of the role of FGF21 in OS in humans with CKD and T2D; mechanistic studies to explain the association of serum FGF21 with oxidative stress in CKD are needed.

A risk score to predict admission to the intensive care unit in patients with Covid-19: the ABC-GOALS score / Puntaje de riesgo para predecir el ingreso a una unidad de cuidados intensivos en pacientes con Covid-19: puntaje ABC-GOALS

Abstract: Objective: To develop a score to predict the need for intensive care unit (ICU) admission in Covid-19. Materials and methods: We assessed patients admitted to a Covid-19 center in Mexico. Patients were segregated into a group that required ICU admission, and a group that never required ICU admission. By logistic regression, we derived predictive models including clinical, laboratory, and imaging findings. The ABC-GOALS was constructed and compared to other scores. Results: We included 329 and 240 patients in the development and validation cohorts, respectively. One-hundred-fifteen patients from each cohort required ICU admission. The clinical (ABC-GOALSc), clinical+laboratory (ABC-GOALScl), clinical+laboratory+image (ABC-GOALSclx) models area under the curve were 0.79 (95%CI=0.74-0.83) and 0.77 (95%CI=0.71-0.83), 0.86 (95%CI=0.82-0.90) and 0.87 (95%CI=0.83-0.92), 0.88 (95%CI=0.84-0.92) and 0.86 (95%CI=0.81-0.90), in the development and validation cohorts, respectively. The ABC-GOALScland ABC-GOALSclxoutperformed other Covid-19 and pneumonia predictive scores. Conclusion: ABC-GOALS is a tool to timely predict the need for admission to ICU in Covid-19.

Resumen: Objetivo: Desarrollar un puntaje predictivo de la necesidad de ingreso a una unidad de cuidados intensivos (UCI) en Covid-19. Material y métodos: Se evaluaron pacientes ingresados por Covid-19 en México. Se dividieron en un grupo que requirió ingreso a UCI y un grupo que nunca lo requirió. Se derivaron modelos predictivos incluyendo variables clínicas, de laboratorio e imagen y se integraron en el puntaje ABC-GOALS. Resultados: Se incluyeron 329 y 240 pacientes en cohortes de desarrollo y validación, respectivamente. Ciento quince pacientes de cada cohorte requirieron ingreso a UCI. Las áreas bajo la curva de los modelos clínico (ABC-GOALSc), clínico+laboratorio (ABC-GOALScl), clínico+laboratorio+imagen (ABC-GOALSclx) fueron 0.79 (IC95%=0.74-0.83) y 0.77 (IC95%=0.71-0.83); 0.86 (IC95%=0.82-0.90) y 0.87 (IC95%=0.83-0.92); 0.88 (IC95%=0.84-0.92) y 0.86 (IC95%=0.81-0.90) en las cohortes de derivación y validación, respectivamente. El desempeño del ABC-GOALS fue superior a otros puntajes de riesgo. Conclusión: ABC-GOALS es una herramienta para predecir oportunamente la necesidad de ingreso a UCI en Covid-19.

Association Between Urinary Epidermal Growth Factor and Renal Prognosis in Lupus Nephritis.

OBJECTIVE: To evaluate the role of urinary epidermal growth factor (EGF) as a biomarker of chronic kidney damage in lupus nephritis (LN). METHODS: A proteomics approach was used to identify urinary EGF as a biomarker of interest in a discovery cohort of patients with LN. The expression of urinary EGF was characterized in 2 large multiethnic LN cohorts, and the association between urinary EGF levels at the time of flare and kidney outcomes was evaluated in a subset of 120 patients with long-term follow-up data. For longitudinal studies, the expression of urinary EGF over time was determined in 2 longitudinal cohorts of patients with LN from whom serial urine samples were collected. RESULTS: Discovery analysis showed the urinary EGF levels as being low in patients with active LN (median peptide count 8.4, interquartile range [IQR] 2.8-12.3 in patients with active LN versus median 48.0, IQR 45.3-64.6 in healthy controls). The peptide sequence was consistent with that of proEGF, and this was confirmed by immunoblotting. The discovery findings were verified by enzyme-linked immunosorbent assay. Patients with active LN had a significantly lower level of urinary EGF compared to that in patients with active nonrenal systemic lupus erythematosus (SLE), patients with inactive SLE, and healthy kidney donors (each P < 0.05). The urinary EGF level was inversely correlated with the chronicity index of histologic features assessed in kidney biopsy tissue (Spearman's r = -0.67, P < 0.001). Multivariate survival analysis showed that the urinary EGF level was associated with time to doubling of the serum creatinine level (DSCr), a marker of future end-stage kidney disease (ESKD) (hazard ratio 0.88, 95% confidence interval 0.77-0.99, P = 0.045). Patients whose LN symptoms progressed to DSCr and those who experienced progression to ESKD had a lower urinary EGF level at the time of flare, and urinary EGF levels decreased over the 12 months following flare. All patients who experienced progression to ESKD were identified based on a urinary EGF cutoff level of <5.3 ng/mg. CONCLUSION: Urinary EGF levels are correlated with histologic kidney damage in patients with LN. Low urinary EGF levels at the time of flare and decreasing urinary EGF levels over time are associated with adverse long-term kidney outcomes.

Use of the Tissue Common Rejection Module Score in Kidney Transplant as an Objective Measure of Allograft Inflammation.

Long-term kidney transplant (KT) allograft outcomes have not improved as expected despite a better understanding of rejection and improved immunosuppression. Previous work had validated a computed rejection score, the tissue common rejection module (tCRM), measured by amplification-based assessment of 11 genes from formalin-fixed paraffin-embedded (FFPE) biopsy specimens, which allows for quantitative, unbiased assessment of immune injury. We applied tCRM in a prospective trial of 124 KT recipients, and contrasted assessment by tCRM and histology reads from 2 independent pathologists on protocol and cause biopsies post-transplant. Four 10-µm shaves from FFPE biopsy specimens were used for RNA extraction and amplification by qPCR of the 11 tCRM genes, from which the tCRM score was calculated. Biopsy diagnoses of either acute rejection (AR) or borderline rejection (BL) were considered to have inflammation present, while stable biopsies had no inflammation. Of the 77 biopsies that were read by both pathologists, a total of 40 mismatches in the diagnosis were present. The median tCRM scores for AR, BL, and stable diagnoses were 4.87, 1.85, and 1.27, respectively, with an overall significant difference among all histologic groups (Kruskal-Wallis, p < 0.0001). There were significant differences in tCRM scores between pathologists both finding inflammation vs. disagreement (p = 0.003), and both finding inflammation vs. both finding no inflammation (p < 0.001), along with overall significance between all scores (Kruskal-Wallis, p < 0.001). A logistic regression model predicting graft inflammation using various clinical predictor variables and tCRM revealed the tCRM score as the only significant predictor of graft inflammation (OR: 1.90, 95% CI: 1.40-2.68, p < 0.0001). Accurate, quantitative, and unbiased assessment of rejection of the clinical sample is critical. Given the discrepant diagnoses between pathologists on the same samples, individuals could utilize the tCRM score as a tiebreaker in unclear situations. We propose that the tCRM quantitative score can provide unbiased quantification of graft inflammation, and its rapid evaluation by PCR on the FFPE shave can become a critical adjunct to help drive clinical decision making and immunosuppression delivery.

High frequency of nocturnal hypertension in lupus nephritis: should ABPM be implemented in usual practice?

INTRODUCTION/OBJECTIVES: Hypertension management in lupus nephritis (LN) is guided by in-office blood pressure (BP); however, recent studies demonstrate that lupus patients frequently have nocturnal hypertension and reduced BP dipping. The aim of the study was to evaluate 24-h blood pressure in patients with active LN and after response to treatment. METHODS: Seventy active LN patients were evaluated during a LN flare by ambulatory blood pressure monitoring (ABPM). Later, 10 patients with complete response were re-evaluated after 12 months along with 20 matched controls. Overall, daytime and nightime BP, day-to-night dipping, BP load and variability, and the incidence of abnormal BP patterns were assessed. Blood pressure levels were correlated with clinical and histologic parameters and independent associations evaluated by linear regression. RESULTS: Overall systolic hypertension occurred in 25 (36%) patients and diastolic hypertension in 28 (40%). Nighttime systolic and diastolic hypertension occurred in 35 (50%) and 44 (63%) of patients, respectively. Nocturnal systolic day-to-night BP decrease was abnormal in 59 (84%) patients. Only 18 (26%) were diagnosed with HT by in-office evaluation while 29 (41%) had masked hypertension (MH)/masked uncontrolled hypertension (MUCH), and 3 (4%) had white coat hypertension. Patients with MH had lower eGFR, complement C3, hemoglobin, and higher systolic variability compared with patients with normal BP. Systolic and diastolic BP levels were associated with the years under corticosteroid treatment, activity biomarkers (proteinuria, complement C3), and the degree of interstitial inflammation in the kidney biopsy. A re-evaluation at 12 months showed that although 9 out of 10 patients had normal in-office BP and BP loads improved, still 5 patients remained with MH due to nocturnal hypertension, and 7 remained with abnormal day-to-night dipping. These numbers were higher than those of matched controls. CONCLUSIONS: Due to the high frequency of nocturnal hypertension and abnormal day-to-night dipping, office BP measurements alone may not be sufficient to guide hypertension management in patients with LN.Key Points• Nocturnal hypertension and abnormal BP patterns are frequent and not detectable by the standard in-office BP evaluation in LN patients.• BP abnormalities may not be fully corrected after a complete clinical response to treatment in lupus nephritis and are only detectable by ABPM.• The degree of interstitial inflammation in the kidney biopsy in LN patients is associated to BP levels. This supports the hypotheses underlining the role of interstitial inflammation in salt sensitivity and hypertension.

Treatment strategies and outcome of parvovirus b19 infection in kidney transplant recipients: a case series and literature review of 128 patients.

Abstract Background There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. Objective The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. Methods We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. Results In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. Conclusions In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.

LECT2 Amyloidosis in Kidney Transplantation: A Report of 5 Cases.

Leukocyte chemotactic factor 2 (LECT2) amyloidosis is a recently recognized entity that often affects the kidneys. Little information is available regarding kidney transplant outcomes in patients with LECT2 amyloidosis or who received kidney allografts containing LECT2 amyloid. We present clinical findings and allograft outcomes of 5 patients who received kidneys with donor-derived LECT2 amyloidosis. In all 5, LECT2 amyloidosis was discovered during protocol biopsies or in evaluation of suspected rejection. Less than 10% of kidney parenchyma was involved, with mostly interstitial and vascular deposits. Allograft function was not impaired and the amyloid deposits persisted for up to 8 years of follow-up. We conclude that kidneys with limited and localized LECT2 amyloid deposits that are otherwise suitable for transplantation need not be automatically discarded.

Capillary leak syndrome as a complication of antibody-mediated rejection treatment: a case report.

We report a case of capillary leak that developed during treatment of antibody-mediated rejection in a kidney transplant recipient. A 53-year-old female transplant recipient experienced an increase in serum creatinine from 1.1 to 1.8 mg/dL. Antibody-mediated rejection was diagnosed by graft biopsy. She was treated with five plasmapheresis sessions (on alternate days with albumin replacement), five doses of immunoglobulin (5 g/dose at 100 mg/kg), a single dose of rituximab (500 mg), and four doses of bortezomib on days 1, 4, 7, and 10 (1.72 mg/dose at 1.3 mg/m2 body surface area). During treatment, edema, slight diarrhea, pancytopenia, hypoalbuminemia, peripheral neuropathy, and postural hypotension were noted. Despite control of liquids, she presented with edema progressing to an increase of more than 10 kg body weight. Prerenal acute graft dysfunction associated with hypotension was diagnosed on day 12, heart failure or other infectious complications being discounted. On day 13, daily hemodialysis was prescribed, and a stable volume status was reached after five hemodialysis sessions. On day 20, the patient recovered diuresis and the edema and diarrhea abated, but she remained on chronic hemodialysis. After excluding other causes of distributive shock, the diagnosis of capillary leak syndrome was based on the presence of hypotension, generalized edema, and hypoalbuminemia in the absence of significant proteinuria. The concomitant presence of diarrhea, peripheral neuropathy, and pancytopenia, suggest a possible causal role for bortezomib. Awareness by clinicians of capillary leak syndrome associated with bortezomib-based treatment of AMR is paramount, despite its rarity.

Simple risk score for prediction of haemorrhagic complications after a percutaneous renal biopsy.

AIM: To derive a simple risk score to predict the individual risk of major complications for patients undergoing a percutaneous renal biopsy procedure of native kidneys. METHODS: The risk score was derived from a cohort of 1205 adult patients subjected to percutaneous renal biopsy and assigned to training and validation datasets. Factors associated with major complications were derived from univariate analysis and then modelled by stepwise multivariate logistic regression. Based on the odds ratio, independent predictors were assigned a weighted integer. The risk score is calculated from the sum of the integers. RESULTS: The overall incidence of major complications was 3.2%. Independent factors associated with MC were lower pre-biopsy haemoglobin, lower platelets, higher blood urea nitrogen, documented chronic kidney disease features in pre-biopsy ultrasound (US) and the presence of haematoma in the post-biopsy US. A score for pre-biopsy evaluation included the first four predictors and stratified patients in three categories with increasing risk at higher scores (low-risk 0.1%, moderate-risk 3.0% and high-risk 26.1%). The score demonstrated good discriminative power (AUC = 0.872). The addition of post-biopsy US findings increased the discriminative power (AUC = 0.938). A higher post-biopsy risk score was also associated with a higher incidence of MC (low-risk 0.2%, moderate-risk 2.7%, high-risk 16.9%). CONCLUSION: The risk of major complications after a percutaneous renal biopsy can be assessed by a simple risk score calculated from readily available information.

Biopsy-proven renal involvement and prognosis in 13 hispanic patients with primary Sjögren syndrome. / Afección renal confirmada mediante biopsia y pronóstico en 13 pacientes hispanos con síndrome de Sjögren primario.

BACKGROUND: The aim of this study was to describe a case series of 13 Hispanic patients with primary Sjögren syndrome (pSS) and biopsy-proven renal involvement. METHODS: We describe the clinical, serological and histological characteristics as well as the prognosis in a group of patients with pSS and biopsy-proven renal involvement, treated in 2 referral nephrology units in Mexico City. RESULTS: Thirteen patients with pSS underwent kidney biopsy (KB) over a period of 27 years. The median duration from pSS diagnosis to KB was 13.9 months. Seven patients (54%) had glomerulonephritis and 6 patients (46%) had tubulointerstitial nephritis. All patients were treated with corticosteroids and/or immunosuppressants. Eight patients (62%) remained stable or their renal function improved after a median follow-up of 12 months. CONCLUSIONS: This case series reflects the broad spectrum of renal involvement in pSS. We observed that in our Hispanic population, glomerular involvement was the most frequent abnormality, mainly membranous glomerulopathy, followed by tubulointerstitial disease. Tubular atrophy and interstitial fibrosis were also common biopsy findings. Treatment with corticosteroids or other immunosuppressive agents appear to slow renal disease progression.

Efectos renales y nefroprotección inducidos por el inhibidor del SGLT2 Empagliflozina en pacientes con diabetes mellitus: revisión de la literatura / Renal effects and nephroprotection induced by SGLT2 inhibitor Empagliflozin in patients with Diabetes Mellitus: a literature review

La insuficiencia renal es una comorbilidad frecuente en pacientes con diabetes mellitus (DM) e incrementa en ellos el riesgo cardiovascular; la hiperglucemia crónica en pacientes con DM induce una gran cantidad de alteraciones directas e indirectas en la estructura y la función renal, y constituye el principal factor para el desarrollo de la nefropatía diabética y la enfermedad renal terminal. En la presente revisión, se exponen los resultados de los estudios en los que se ha demostrado la alta tolerabilidad de empagliflozina en pacientes diabéticos con insuficiencia renal concomitante en estadios I a III. Empagliflozina, mediante la inhibición de SGLT2, ofrece una terapia novedosa con efectos benéficos no sólo sobre el control glucémico, sino también beneficios cardiovasculares y renales, los cuales han sido demostrados en el estudio EMPA-REG OUTCOME y continúan en evaluación en otros estudios

Chronic kidney disease is a frequent comorbidity in patients with diabetes mellitus (DM) and it increases their cardiovascular risk; chronic hyperglycemia in patients with DM leads to direct and indirect disorders in kidney's structure and function, and it is the principal risk factor for the development of diabetic nephropathy and end-stage renal disease. In the current review, results of studies are exposed in which high tolerability of empagliflozin is exposed in diabetic patients with kidney disease. Empagliflozin by inhibiting SGLT2 provides a novel therapy with benefic effects, not only in glycemic control, but it also has cardiovascular and renal benefits, which they have been demonstrated in the EMPA-REG OUTCOME trial, and continue in evaluation in other studies

Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement.

Several classification schemes have been developed for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with actual debate focusing on their clinical and prognostic performance. Sixty-two patients with renal biopsy-proven AAV from a single center in Mexico City diagnosed between 2004 and 2013 were analyzed and classified under clinical (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], renal limited vasculitis [RLV]), serological (proteinase 3 anti-neutrophil cytoplasmic antibodies [PR3-ANCA], myeloperoxidase anti-neutrophil cytoplasmic antibodies [MPO-ANCA], ANCA negative), and histopathological (focal, crescenteric, mixed-type, sclerosing) categories. Clinical presentation parameters were compared at baseline between classification groups, and the predictive value of different classification categories for disease and renal remission, relapse, renal, and patient survival was analyzed. Serological classification predicted relapse rate (PR3-ANCA hazard ratio for relapse 2.93, 1.20-7.17, p = 0.019). There were no differences in disease or renal remission, renal, or patient survival between clinical and serological categories. Histopathological classification predicted response to therapy, with a poorer renal remission rate for sclerosing group and those with less than 25 % normal glomeruli; in addition, it adequately delimited 24-month glomerular filtration rate (eGFR) evolution, but it did not predict renal nor patient survival. On multivariate models, renal replacement therapy (RRT) requirement (HR 8.07, CI 1.75-37.4, p = 0.008) and proteinuria (HR 1.49, CI 1.03-2.14, p = 0.034) at presentation predicted renal survival, while age (HR 1.10, CI 1.01-1.21, p = 0.041) and infective events during the induction phase (HR 4.72, 1.01-22.1, p = 0.049) negatively influenced patient survival. At present, ANCA-based serological classification may predict AAV relapses, but neither clinical nor serological categories predict renal or patient survival. Age, renal function and proteinuria at presentation, histopathology, and infectious complications constitute the main outcome predictors and should be considered for individualized management.