Epidemiological, immunological, and treatment response profile of patients with lupus nephritis in Brazil.

BACKGROUND AND HYPOTHESIS: Brazil has the largest number of individuals of African descent outside Africa and a very admixed population. Among cases of lupus nephritis (LN) in the country, there are differences in incidence, and even in severity, depending on the location and characteristics of the population studied. The aim of this study was to describe the clinical and epidemiological characteristics of LN in Brazil, as well as to determine which of those characteristics would be risk factors for a poor renal prognosis. METHODS: This was a retrospective, descriptive observational study of patients diagnosed with LN who underwent kidney biopsy between 1999 and 2015 in the Nephrology Department of the Hospital das Clínicas, in São Paulo, Brazil. Data were collected from electronic medical records. RESULTS: We evaluated 398 patients, among who 94.1% and 77.7% tested positive for antinuclear antibodies and anti-DNA antibodies, respectively, whereas 33.7% showed the full-house pattern. The time from LN symptom onset to biopsy was <6 months in 47.5% (early biopsy group) and ≥6 months in 52.5% (late biopsy group). In the early biopsy group, the chronicity index was lower and the activity index was higher. Multivariate analysis showed that a higher chronicity index was the only independent risk factor for progression to requiring kidney replacement therapy. CONCLUSION: Late biopsy seems to be associated with negative renal outcomes in LN. However, it seems that a higher chronicity index is the main predictor of a poor renal outcome among patients with LN in Brazil.

Diagnosis and Course of Membranous Nephropathy in Adults: Comparison by Age Group.

INTRODUCTION: There have been few studies comparing younger and older adults with membranous nephropathy. The objective of this study was to compare younger and older patients with membranous nephropathy, in terms of the clinical, etiological, remission, and survival data. METHOD: This was a retrospective study of patients with membranous nephropathy who underwent renal biopsy between 2009 and 2017. RESULTS: We included 214 patients with membranous nephropathy. At diagnosis, 169 (79%) of those patients were <60 years of age and 45 (21%) were ≥60 years of age. There was a predominance of males in both groups. The degree of proteinuria and the prevalence of hematuria did not differ significantly between the groups. However, the median serum creatinine level was higher in the ≥60-year group as was the prevalence of hypertension. Of the patients evaluated, 36 (16.8%) had secondary membranous nephropathy. Although the proportions of infectious and autoimmune causes were comparable between the two groups, neoplastic etiologies were more common in the ≥60-year group. A total of 86 in the <60-year group and 25 in the ≥60-year group were followed long term, and partial or complete remission was achieved in 68.5% and 68.0% of the younger and older patients, respectively. However, whom progressed to requiring dialysis eight (9.3%) were in the <60-year group patients and eight (32.0%) of the ≥60-year group patients (p = 0.0045). CONCLUSION: Despite having worse renal function at diagnosis, older patients with membranous nephropathy appear to have remission rates comparable to those of younger patients with the disease, which demonstrates the benefits of seeking diagnosis and treatment.

Evaluating TIMP-2 and IGFBP-7 as a predictive tool for kidney injury in ureteropelvic junction obstruction.

A major challenge in the management of ureteropelvic junction obstruction (UPJO) is the selection of patients who would benefit from surgical treatment. Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) indicate renal cell stress and are associated with cell cycle arrest. The [TIMP-2] [IGFBP7] ratio (Nephrocheck®) has been recently applied in patients in intensive care units patients to predict the development of acute kidney injury. In this study, we evaluated the performance of these biomarkers performance to distinguishing obstructive hydronephrosis (HN) from non-obstructive HN. MATERIALS AND METHODS: Consecutive patients with UPJO were enrolled in this study. Urinary [TIMP-2] [IGFBP7] and clinical characteristics (hydronephrosis grade, differential renal function, and drainage half-time) were measured in the following groups: 26 children with obstructive HN at initial diagnosis (group 1A) and after six months of dismembered pyeloplasty (group 1B); 22 children with non-obstructive HN (group 2), and 26 children without any urinary tract condition, as the control group (group 3). RESULTS: Comparing the initial samples, [TIMP-2] [IGFBP7] had higher levels in the HN groups and lower levels in the control group; however, no difference was observed between the HN groups (obstructive vs. non-obstructive). After six months of follow-up, patients who underwent dismembered pyeloplasty showed stability in the urinary concentration of [TIMP-2] [IGFBP7]. All patients with [TIMP-2] [IGFBP7] higher than 1.0 (ng/mL)2/1000 had diffuse cortical atrophy on ultrasonography. CONCLUSIONS: We showed that urinary levels of urinary [TIMP-2] [IGFBP7] are higher in children with HN than controls. Nephrocheck® is not reliable in predicting the need for surgical intervention for pediatric patients with UPJO.

Renal Outcomes in Brazilian Patients with Immunoglobulin A Nephropathy and Cellular Crescentic Lesions.

BACKGROUND AND AIM: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy. The Oxford classification was recently updated to include crescents as markers of poor prognosis. The aim of this study was to evaluate the impact of cellular crescents on the prognosis of patients with IgAN in Brazil. METHODS: This was a single-centre retrospective analysis of medical records and renal biopsies in patients with IgAN. The renal biopsy findings were classified according to the revised Oxford classification: mesangial hypercellularity, endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy or interstitial fibrosis (T), and crescent formation (C). We evaluated a composite outcome (progression to end-stage renal disease or creatinine doubling). We performed analyses between the patients with crescents in the renal biopsy specimen (C1/C2 group) and those without such crescents (C0 group). RESULTS: We evaluated 111 patients, of whom 72 (65.0%) were women, 80 (72.0%) self-identified as White, 73 (65.6%) were hypertensive, and 95 (85.6%) had haematuria. The distribution of patients according to cellular crescentic lesions was: C0, 80 (72%); C1, 27 (24.4%); C2, 4 (3.6%). The composite outcome was observed in 33 (29.72%) of the 111 patients. In comparison with the C0 group, the C1/C2 group had higher proportions of patients with hypertension (p = 0.04), haematuria (p = 0.03), worse serum creatinine (p = 0.0007), and worse estimated glomerular filtration rate (p = 0.0007). The C1/C2 group also had higher proportions of patients in whom the biopsy specimen was classified as E1 (p = 0.009), S1 (p = 0.001), or T1/T2 (p = 0.03), In addition, the mean follow-up period was shorter in the C1/C2 group (p < 0.0001). Furthermore, the composite outcome was observed in a greater proportion of patients and in a shorter length of time in the C1/C2 group than in the C0 group (p = 0.002 and p = 0.0014, respectively). In a Cox regression analysis, the independent risk factors for the composite outcome had Oxford classifications of S1, T1/T2, and C1/C2. CONCLUSION: Oxford classification findings of S1, T1/T2, or C1/C2 were independent risk factors for the composite outcome, corroborating previous studies.

Mortality of Patients on Maintenance Hemodialysis Submitted to Coronary Artery Bypass Surgery.

BACKGROUND: Patients with chronic kidney disease (CKD) are less likely to be submitted to coronary artery bypass grafting (CABG) then clinical medical treatment based on the potential high risk of mortality. However, whether patients on maintenance dialysis who underwent an elective CABG experience high hospital- and long-term mortality is still debatable. METHODS: This is a prospective observational study that evaluated patients who underwent elective CABG. Three groups were compared: reference (n = 167, estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2), CKD3-4 (n = 84, eGFR 15-59 mL/min/1.73 m2), and maintenance hemodialysis (n = 31). Demographic, clinical, biochemical, fluid balance data, and Sequential Organ Failure Assessment (SOFA) scores were assessed daily for the same observer from day 1 (surgery) to hospital discharge. RESULTS: The main outcomes were in-hospital and 1-year mortality. Patients aged 63 ± 10, 63 ± 8, and 65 ± 6 years old, in reference, CKD3-4, and dialysis groups, respectively (p = 0.605). Patients from the reference group had a lower prevalence of diabetes (p = 0.010) and hypertension (p = 0.021). SOFA scores were higher in CKD3-4 and dialysis groups (p = 0.001), though this difference disappeared without the renal component (p = 0.326). In-hospital mortality (n = 17) was similar across groups (p = 0.955). There was no difference in 1-year mortality among groups even after adjustments for age, diabetes, intraoperative blood loss, and time on ventilation. CONCLUSIONS: CABG short-term mortality seems not to be greater among selected patients on maintenance dialysis. A multidisciplinary team has been helping cardiologists and cardiac surgeons in the decision-making process regarding the best approach in coronary artery disease, and CABG should be considered a worthy therapeutic option.

Atypical presentation of acute post-infectious glomerulonephritis in patients with sickle cell disease: report of two cases.

BACKGROUND: Sickle cell disease (SCD) is a highly prevalent genetic disease worldwide. In the natural evolution of SCD, glomerular lesions can develop, presenting histopathological patterns of segmental or focal membranoproliferative glomerulosclerosis, with or without thrombotic microangiopathy. We report two cases of acute post-infectious glomerulonephritis (APIGN), with atypical presentations, in patients with SCD. CASE PRESENTATION: Case 1: An 18-year-old female with SCD presented with a 21-day history of progressive oedema, accompanied by dyspnoea, productive cough, fever, and chest pain. Blood tests showed the following: haemoglobin 6.1 g/dl; leucocytes 18,820 cells/mm3; and creatinine 0.49 mg/dl. A urine sample evidenced leucocyturia and haematuria. The 24-h proteinuria was 8.99 g, serum albumin level was 1.2 g/dl, low serum C3 levels and high levels of anti-streptolysin O. Renal biopsy was consistent with APIGN. The patient was treated with diuretic and anti-proteinuric agents, subsequently evolving to reversal of the renal alterations. Case 2: A 12-year-old male with SCD presented with a 20-day history of a non-productive cough and progressive oedema, together with hypertension. The serum creatinine concentration was 0.48 mg/dl. A urine sample evidenced leukocyturia and haematuria. The 24-h proteinuria was 12.5 g, and the serum albumin level was 2.6 g/dl. The levels of C3 and C4 were normal. Renal biopsy revealed APIGN. The patient was treated with diuretic and anti-proteinuric agents, subsequently evolving reversal of the renal alterations. CONCLUSIONS: The presentation of the two cases reported here are not typical of SCD-related kidney injury. Analysis of the renal biopsy specimens elucidated the diagnosis, affecting the prognosis, because that of APIGN is highly favourable, unlike that of nephrotic syndrome associated with SCD glomerulopathy.

Acute kidney injury in Latin America: a view on renal replacement therapy resources.

BACKGROUND: Acute kidney injury (AKI) has increasingly been recognized as an important public health issue due to its rising frequency, its associations with early and late adverse outcomes and its economic burden. METHODS: Given the importance of determining the available resources to address this serious issue, the AKI Committee of SLANH conducted a survey to obtain information about infrastructure, human resources and equipment devoted to the treatment of AKI in Latin America RESULTS: A total of 246 units from 14 countries participated in the survey, the majority of them pertaining to nephrology divisions in teaching hospitals. Intermittent hemodialysis was universally performed by all of the units, and less frequently, slow extended dialysis (40%) and continuous renal replacement therapy (23%) were performed. Seventy-nine units (30%) perform peritoneal dialysis, but only 51 (19%) of them reported having treated at least 1 patient with this technique in the last 3 months pre-survey. The vast majority of the units reported adequate water treatment and use of modern filter membranes. Most of the patients received renal replacement therapy (RRT) in the intensive care unit. Specific causes of AKI were reported in different frequencies, with a heterogeneous pattern among the countries. Septic abortion, hemolytic-uremic syndrome, community-acquired diarrhea and leptospirosis were the etiologies most frequently associated with AKI. CONCLUSIONS: To our knowledge, this report was the first available study of the equipment and human resources utilized for RRT in AKI patients in Latin America.

Urinary CD80 and Serum suPAR as Biomarkers of Glomerular Disease among Adults in Brazil.

INTRODUCTION: Urinary CD80 has been shown to have good specificity for minimal change disease (MCD) in children. However, the investigation of circulating factors such as soluble urokinase plasminogen activator receptor (suPAR) as biomarkers of focal segmental glomerulosclerosis (FSGS) is quite controversial. The objective of this study was to determine whether urinary CD80 and serum suPAR can be used for the diagnosis of MCD and FSGS, respectively, in the adult population of Brazil. We also attempted to determine whether those biomarkers assess the response to immunosuppressive treatment. METHODS: This was a prospective study in which urine and blood samples were collected for analysis of CD80 and suPAR, respectively, only in the moment of renal biopsy, from patients undergoing to diagnostic renal biopsy. At and six months after biopsy, we analyzed serum creatinine, serum albumin, and proteinuria in order to evaluate the use of the CD80 and suPAR collected in diagnosis as markers of response to immunosuppressive treatment. In healthy controls were collected urinary CD80 and proteinuria, serum suPAR, and creatinine. RESULTS: The results of 70 renal biopsies were grouped, by diagnosis, as follows: FSGS (n = 18); membranous nephropathy (n = 14); MCD (n = 5); and other glomerulopathies (n = 33). There was no significant difference among the groups in terms of the urinary CD80 levels, and serum suPAR was not significantly higher in the FSGS group, as would have been expected. Urinary CD80 correlated positively with nephrotic syndrome, regardless of the type of glomerular disease. Neither biomarker correlated with proteinuria at six months after biopsy. CONCLUSION: In adults, urinary CD80 can serve as a marker of nephrotic syndrome but is not specific for MCD, whereas serum suPAR does not appear to be useful as a diagnostic or treatment response marker.

Advanced prostate cancer as a cause of oncogenic osteomalacia: an underdiagnosed condition.

PURPOSE: Tumor-induced osteomalacia (TIO) is a paraneoplastic bone mineral disturbance related to fibroblast growth factor 23 (FGF23) overproduction by the tumor, usually from mesenchymal origin. Such condition leads to high phosphate renal wasting and, consequently, to cumbersome symptoms as weakness, bone pain, and fractures. METHOD: Case report. RESULT: We report a case of an advanced castration-refractory prostate cancer patient, which developed severe hypophosphatemia with elevated phosphate excretion fraction. TIO was suspected, and increased levels of FGF23 reinforced such diagnosis. The patient died 4 months after being diagnosed with TIO. CONCLUSION: This case suggests that TIO has a dismal prognosis in prostate cancer patients. The clinical oncology community must be aware about such disturbance that can be present in those patients with weakness, bone pain, and hypophosphatemia.

IgA nephropathy in patients with serum anti-neutrophil cytoplasmic autoantibody (ANCA) positivity: case series.

Some cases of patients with IgA nephropathy diagnosed via kidney biopsy and antineutrophil cytoplasmic antibody (ANCA) positivity have been reported. This article describes a case series comprising patients with IgA nephropathy and ANCA positivity seen at a medical center in the city of São Paulo, Brazil, from 1996 to 2016. A total of 111 patients underwent diagnostic kidney biopsies for IgA nephropathy. Five were ANCA-positive at the time of diagnosis; their mean age was 45 ± 15.3 years and they were predominantly females with a mean proteinuria of 2.2 ± 0.9 g/day and a median serum creatinine level of 2.5 (2.0 - 8,6) mg/dL; all had hematuria. Four of the five were cANCA-positive (80%); all had normal serum C3 and C4 levels; and 80% were positive for ANA. One case presented an association with infection, but no associations were found with medication. One patient had granuloma and another had a collapsing lesion. This article describes the cases of five ANCA-positive patients (with predominantly cANCA positivity) submitted to diagnostic kidney biopsies for IgA nephropathy; one patient had a collapsing lesion, but progressed well.

Acute kidney injury and renal replacement therapy: terminology standardization.

The Department of Acute Kidney Injury (IRA) of the Brazilian Society of Nephrology prepared this document for the purpose of standardizing AKI terminology and dialysis modalities in the Portuguese language for Brazil. Several terms with similar meanings have been used in AKI and its dialysis modalities, causing confusion and disparities among patients, nephrologists, health institutions, private care companies, insurance companies and government entities. These disparities can impact medical care, hospital organization and care, as well as the funding and reimbursement of AKI-related procedures. Thus, consensual nomenclature and definitions were developed, including the definitions of AKI, acute kidney disease (AKD) and chronic kidney disease (CKD). Additionally, we addressed all dialysis modalities and extracorporeal procedures related to AKI, currently approved and available in the country. The Brazilian Society of Nephrology hopes that this Consensus can standardize the terminology and provide technical support to all involved in AKI care in Brazil.

Determination of Anti-Phospholipase A2 and Anti-Thrombospondin Type 1 Domain-Containing Protein 7A in Latin Patients with Membranous Nephropathy.

Primary membranous nephropathy (MN) is caused by antibodies against podocyte antigens, especially the type M receptor of phospholipase A2 (PLA2R) and thrombospondin type-1 domain containing 7 A (THSD7A). This study's aim was the determination of anti-PLA2R, anti-THSD7A serum antibodies, and anti-PLA2R renal tissue staining prevalence in a Latin population with MN, as well as evaluating their role as biomarkers for disease activity. The performance of the two anti-PLA2R serum diagnostic methods-ELISA and indirect immunofluorescence (IFI)-was evaluated for the diagnosis of MN. Fifty-nine patients, including 29 with MN, 18 with lupus membranous nephropathy (LMN) and 12 with focal and segmental glomerulosclerosis (FSGS), were evaluated for serum antibodies. Renal biopsies were also evaluated for the presence of anti-PLA2R staining. Twenty-one patients with MN were followed for 1 year. Patients with LMN and FSGS were negative for both antibodies. All 29 MN patients were negative for anti-THSD7A; 16 MN patients were positive for anti-PLA2R by ELISA and/or IFI, and 3 MN patients were positive for anti-PLA2R only by IFI. Thus, the anti-PLA2R ELISA test demonstrated 45% sensitivity and 97% specificity, while the IFI test showed, respectively, 55% and 100% in our MN patients. Among the 28 MN renal biopsies, 20 presented anti-PLA2R positive staining, corresponding to a 72% sensitivity. Positive correlations were observed between the anti-PLA2R ELISA titer and proteinuria. In conclusion, determination of anti-PLA2R antibodies in the MN Latin population showed similar rates to those reported for other populations. The anti-PLA2R serum levels correlated with MN disease activity.

Latin American registry of renal involvement in COVID-19 disease. The relevance of assessing proteinuria throughout the clinical course.

The Latin American Society of Nephrology and Hypertension conducted a prospective cohort, multinational registry of Latin American patients with kidney impairment associated to COVID-19 infection with the objective to describe the characteristics of acute kidney disease under these circumstances. The study was carried out through open invitation in order to describe the characteristics of the disease in the region. Eight-hundred and seventy patients from 12 countries were included. Median age was 63 years (54-74), most of patients were male (68.4%) and with diverse comorbidities (87.2%). Acute kidney injury (AKI) was hospital-acquired in 64.7% and non-oliguric in 59.9%. Multiorgan dysfunction syndrome (MODS) due to COVID-19 and volume depletion were the main factors contributing to AKI (59.2% and 35.7% respectively). Kidney replacement therapy was started in 46.2%. Non-recovery of renal function was observed in 65.3%. 71.5% of patients were admitted to ICU and 72.2% underwent mechanical ventilation. Proteinuria at admission was present in 62.4% of patients and proteinuria during hospital-stay occurred in 37.5%. Those patients with proteinuria at admission had higher burden of comorbidities, higher baseline sCr, and MODS was severe. On the other hand, patients with de novo proteinuria had lower incidence of comorbidities and near normal sCr at admission, but showed adverse course of disease. COVID-19 MODS was the main cause of AKI in both groups. All-cause mortality of the general population was 57.4%, and it was associated to age, sepsis as cause of AKI, severity of condition at admission, oliguria, mechanical ventilation, non-recovery of renal function, in-hospital complications and hospital stay. In conclusion, our study contributes to a better knowledge of this condition and highlights the relevance of the detection of proteinuria throughout the clinical course.

Performance of the third-generation models of severity scoring systems (APACHE IV, SAPS 3 and MPM-III) in acute kidney injury critically ill patients.

BACKGROUND: Severity scores are useful to guarantee similar disease severity among groups in clinical trials and to enable comparison between different studies. The aim of this study was to assess the performance of the third generation models of severity scoring systems [simplified acute physiology score (SAPS) 3, acute physiology and chronic health evaluation (APACHE) IV and mortality probability model (MPM)-III] in acute kidney injury (AKI) patients in the intensive care unit (ICU). METHODS: Three hundred and sixty-six consecutive AKI critically ill patients were prospectively assessed in six ICUs of an academic tertiary care center. Scores were applied on AKI diagnosis day (DD) and on the day of nephrology consultation (NCD). Discrimination was assessed by area under the receiver operating characteristic curve (AUCROC) and calibration by Hosmer-Lemeshow (HL) goodness-of-fit test. RESULTS: Hospital mortality rate was 67.8%. SAPS 3 general and Central and South America (CSA) customized equations presented identical good discrimination (AUCROC curve: 0.80 on NCD) and satisfactory HL tests on both analyzed days (P > 0.100). CSA SAPS 3 equation predicted mortality more accurately [standardized mortality ratio (SMR) on NCD = 1.00 (95% confidence interval (CI) 0.84-1.34)]. APACHE IV and MPM-III scores presented similar discrimination compared to SAPS 3 on both analyzed days (P > 0.05). APACHE IV presented satisfactory HL tests over time (P > 0.100) but underestimated mortality [SMR on DD = 1.92 (95% CI 1.61-2.23); SMR on NCD = 1.46 (95% CI 1.48-1.96)]. MPM-III showed unsatisfactory HL test results (P = 0.027 on DD; P = 0.045 on NCD) and underestimated mortality [SMR on NCD = 2.09 (95% CI 1.48-1.96)]. CONCLUSIONS: SAPS 3, especially the geographical customized equation, presented good discrimination and calibration performances, accurately predicting mortality in this group of AKI critically ill patients.

Methimazole-Induced ANCA Vasculitis: A Case Report.

Rapidly progressive glomerulonephritis (RPGN) is a syndrome which presents rapid loss of renal function. Vasculitis represents one of the major causes, often related to anti-neutrophil cytoplasmic antibodies (ANCA). Herein, we report a case of methimazole-induced ANCA-associated vasculitis. A 35-year-old woman complained of weight loss and fatigue for 2 weeks and attended the emergency room with alveolar hemorrhage. She had been diagnosed with Graves' disease and had been taking methimazole in the past 6 months. Her physical examination showed pulmonary wheezing, hypertension and signs of respiratory failure. Laboratory tests revealed urea 72 mg/dL, creatinine 2.65 mg/dL (eGFR CKD-EPI: 20 mL/min/1.73 m2), urine analysis with >100 red blood cells per high-power field, 24 h-proteinuria: 1.3 g, hemoglobin 6.6 g/dL, white-cell count 7700/mm3, platelets 238,000/mm3, complement within the normal range, negative viral serological tests and ANCA positive 1:80 myeloperoxidase pattern. Chest tomography showed bilateral and diffuse ground-glass opacities, and bronchial washing confirming alveolar hemorrhage. A renal biopsy using light microscopy identified 27 glomeruli (11 with cellular crescentic lesions), focal disruption in glomerular basement membrane and fibrinoid necrosis areas, tubulitis and mild interstitial fibrosis. Immunofluorescence microscopy showed IgG +2/+3, C3 +3/+3 and Fibrinogen +3/+3 in fibrinoid necrosis sites. She was subsequently diagnosed with crescentic pauci-immune glomerulonephritis, mixed class, in the setting of a methimazole-induced ANCA vasculitis. The patient was treated with methimazole withdrawal and immunosuppressed with steroids and cyclophosphamide. Four years after the initial diagnosis, she is currently being treated with azathioprine, and her exams show creatinine 1.30 mg/dL (eGFR CKD-EPI: 52 mL/min/1.73 m2) and negative p-ANCA.

Positive fluid balance as an early biomarker for acute kidney injury: a prospective study in critically ill adult patients.

OBJECTIVES: Positive fluid balance is frequent in critically ill patients and has been considered a potential biomarker for acute kidney injury (AKI). This study aimed to evaluate positive fluid balance as a biomarker for the early detection of AKI in critically ill patients. METHODS: This was a prospective cohort study. The sample was composed of patients ≥18 years old who stayed ≥3 days in an intensive care unit. Fluid balance, urinary output and serum creatinine were assessed daily. AKI was diagnosed by the Kidney Disease Improving Global Outcome criteria. RESULTS: The final cohort was composed of 233 patients. AKI occurred in 92 patients (40%) after a median of 3 (2-6) days following ICU admission. When fluid balance was assessed as a continuous variable, a 100-ml increase in fluid balance was independently associated with a 4% increase in the odds of AKI (OR 1.04; 95% CI 1.01-1.08). Positive fluid balance categorized using different thresholds was always significantly associated with subsequent detection of AKI. The mixed effects model showed that increased fluid balance preceded AKI by 4 to 6 days. CONCLUSION: These results suggest that a positive fluid balance might be an early biomarker for AKI development in critically ill patients.

Renal thrombotic microangiopathy associated to worse renal prognosis in Lupus Nephritis.

INTRODUCTION: Renal thrombotic microangiopathy (rTMA) is one of many vascular findings in Lupus Nephritis (LN). However, the influence of rTMA on prognosis has not been well established. The objective of this study was to evaluate the clinical and pathological aspects of patients with lupus and rTMA in kidney biopsy. METHODS: Analysis of medical reports and kidney biopsy of 253 patients with LN, between January 2012 and December 2018. RESULTS: Among our 253 patients, 43 (17%) showed acute or chronic TMA lesions on kidney histology This group had a significantly lower estimated glomerular filtration rate (eGFR) at the time of biopsy (24.1 vs. 64.15 ml/min/1.73m2, p < 0.001), at 1 year of follow up (28.1 vs. 90.7 ml/min/1.73m2, p < 0.001), and at the end of follow up (25.4 vs. 81.55 ml/min/1.73m2, p < 0.001). More patients in the rTMA group reached the composite endpoint of eGFR < 15 mL/min/1.73m2 or death or dialysis (82.9% vs. 32.9%, p < 0.001). When comparing the classical clinical TMA features, the rTMA group had higher percentages of anemia, thrombocytopenia, low haptoglobin levels, but not higher lactate dehydrogenase (LDH) levels (> 214 U/L). Combining these variables in a definition of clinical TMA, the rTMA group had a statistically higher percentage of clinical TMA (20.9% vs. 4.33%, p = 0.001). As expected, TMA group showed higher systolic blood pressure (SBP) (130 vs 129.5 mmHg, p = 0.01). Concerning histopathological features, rTMA group had significantly higher activity (9.0 vs. 6.0, p = 0.001) and chronicity (4.0 vs. 3.0, p = 0.001) scores, also a higher percentage of patients presented with crescents (76.7% vs. 57.1%, p = 0.012). CONCLUSIONS: The classical clinical TMA criteria were unable to predict the presence of tissue TMA, suggesting a probably renal-limited TMA that may occur independently of systemic evident factors. Therefore, renal biopsy remains the critical method for diagnosing an important prognostic feature.

Role of p21 and oxidative stress on renal tubular resistance after acute ischaemic injury.

BACKGROUND: Subsequent ischaemic episodes may induce renal resistance. P21 is a cell cycle inhibitor that may be induced by oxygen-free radicals and may have a protective effect in ischaemic acute kidney injury (AKI). This study aimed at evaluating the role of oxidative stress and p21 on tubular resistance in a model of acquired resistance after renal ischaemia and in isolated renal tubules. METHODS: Wistar rats were divided into: Group 1--sham; Group 2--sham operated and after 2 days submitted to 45-min ischaemia; and Group 3--45-min ischaemia followed after 2 days by a second 45-min ischaemia. Plasma urea was evaluated on Days 0, 2 and 4. Serum creatinine, creatinine clearance and oxidants (thiobarbituric acid-reactive substances) were determined 48 h after the second procedure (Day 4). Histology, immunohistochemistry for lymphocytes (CD3), macrophages (ED1), proliferation (PCNA) and apoptosis (TUNEL) were also evaluated. Rat proximal tubules (PTs) were isolated by collagenase digestion and Percoll gradient from control rats and rats previously subjected to 35 min of ischaemia. PTs were submitted to 15-min hypoxia followed by 45-min reoxygenation. Cell injury was assessed by lactate dehydrogenase release and hydroperoxide production (xylenol orange). RESULTS: Ischaemia induced AKI in Group 2 and 3 rats. Subsequent ischaemia did not aggravate renal injury, demonstrating renal resistance (Group 3). Renal function recovery was similar in Group 2 and 3. Plasma and urine oxidants were similar among in Group 2 and 3. Histology disclosed acute tubular necrosis in Group 2 and 3. Lymphocyte infiltrates were similar among all groups whereas macrophages infiltrate was greater in Group 3. Cell proliferation was greater in Group 2 compared with Group 3. Apoptosis was similar in groups 2 and 3. The p21 expression was increased only in Group 3 whereas it was similar in groups 1 and 2. PTs from the ischaemia group were sensitive to hypoxia but resistant to reoxygenation injury which was followed by lower hydroperoxide production compared to control PT. CONCLUSION: Renal resistance induced by ischaemia was associated with cell mechanism mediators involving oxidative stress and increased p21 expression.

Schistosoma mansoni infection as a trigger to collapsing glomerulopathy in a patient with high-risk APOL1 genotype.

BACKGROUND: Schistosoma mansoni schistosomiasis (SM) remains a public health problem in Brazil. Renal involvement is classically manifested as a glomerulopathy, most often membranoproliferative glomerulonephritis or focal and segmental glomerulosclerosis. We report a case of collapsing glomerulopathy (CG) associated with SM and high-risk APOL1 genotype (HRG). CASE REPORT: A 35-year-old male was admitted for hypertension and an eight-month history of lower-limb edema, foamy urine, and increased abdominal girth. He had a recent diagnosis of hepatosplenic SM, treated with praziquantel, without clinical improvement. Laboratory tests revealed serum creatinine 1.89mg/dL, blood urea nitrogen (BUN) 24mg/dL, albumin 1.9g/dL, cholesterol 531mg/dL, low-density lipoprotein 426mg/dL, platelets 115000/mm3, normal C3/C4, antinuclear antibody (ANA), rheumatoid factor (RF), and antineutrophil cytoplasmic antibodies (ANCA), negative serologies for hepatitis C virus (HCV) and human immunodeficiency virus (HIV), HBsAg negative and AntiHBc IgG positive, no hematuria or leukocyturia, 24 hour proteinuria 6.56g and negative serum and urinary immunofixation. Kidney biopsy established the diagnosis of CG. A treatment with prednisone was started without therapeutic response, progressing to end-stage kidney disease 19 months later. Molecular genetics investigation revealed an HRG. CONCLUSIONS: This is the first report of CG associated with SM in the setting of an HRG. This case highlights the two-hit model as a mechanism for CG pathogenesis, where the high-risk APOL1 genotype exerts a susceptibility role and SM infection serves as a trigger to CG.