RESUMO
BACKGROUND: Pauci-immune necrotizing glomerulonephritis (PING) is commonly associated with the presence of antineutrophilic cytoplasmic antibodies (ANCAs) but a significant number of patients do not have these antibodies. The significance of ANCA-negativity in the context of Berden's classification of PING is not known. METHODS: A retrospective analysis was conducted on all patients with histopathological diagnosis of idiopathic PING irrespective of ANCA status diagnosed between January 1998 to December 2018 and followed up at renal clinic for > 12 months. All biopsies were reclassified by Berden's classification. Clinicopathological characteristics and renal outcomes of ANCA-positive and ANCA-negative patients were compared. RESULTS: Out of 134 patients, 66 (49.5%) were ANCA-negative. The mean age was 34.76 ± 13.3 years. Compared with the ANCA-positive patients, ANCA-negative patients had significantly greater prevalence of nephrotic-range proteinuria (74.23% Vs 57.9%, P = 0.036) with less extra-renal manifestations (P < 0.05)). On histology, focal and crescentic classes dominated with less number of globally sclerosed glomeruli (2.7% Vs 5.07%, P = 0.02) and more mesangial proliferation (22.7% Vs 4.41%, P = 0.002) in the ANCA-negative group, whereas sclerotic was predominant in the ANCA-positive group (P = 0.05). More patients achieved complete and partial recovery in ANCA-negative patients (42.4% Vs 20.5%, P < 0.05) with better renal survival (27.27% Vs 16.17%, log-rank test: P = 0.03) and less patient mortality (13.63% vs 30.8%, log-rank test: P = 0.04) at 2 years. CONCLUSION: Our study confirms high prevalence of ANCA negativity among our cohort and this group presents with isolated renal involvement with better renal and patient survival. The ANCA-positive group showed significantly more patients in the sclerotic class, lower 2-year renal survival, and higher 2-year mortality as compared to the ANCA-negative group. However, the complete and partial responses to treatment were significantly better in the ANCA-negative group. Key Points ⢠This study shows a high prevalence of ANCA negativity in cases of PING in Pakistani population, as almost half of patients in this study did not have these antibodies. ⢠This negativity is more prevalent in the Asian populations but its significance in the context of Berden's classification of PING is unknown. ⢠ANCA-negative group exhibited less severe phenotype and better outcomes compared with ANCA-positive group.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos , Glomerulonefrite , Humanos , Masculino , Feminino , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Rim/patologia , Adulto Jovem , Biópsia , NecroseRESUMO
BACKGROUND: Colorectal cancer (CRC) is a prevalent global malignancy with complex prognostic factors. Tumor-associated macrophages (TAMs) have shown paradoxical associations with CRC survival, particularly concerning the M2 subset. AIM: We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors. METHODS: A cross-sectional study included histopathological assessment of paraffin-embedded tissue blocks obtained from 43 CRC patients. Using CD68 and CD163 immunohistochemistry, we quantified TAMs in tumor stroma and front, focusing on M2 proportion. Demographic, histopathological, and clinical parameters were collected. RESULTS: TAM density was significantly higher at the tumor front, with the M2 proportion three times greater in both zones. The tumor front had a higher M2 proportion, which correlated significantly with advanced tumor stage (P = 0.04), pathological nodal involvement (P = 0.04), and lymphovascular invasion (LVI, P = 0.01). However, no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors. CONCLUSION: Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples. We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage, nodal involvement, and LVI. This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC, warranting further investigation and potential clinical application.
RESUMO
BACKGROUND: Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival. Conventional and novel ultrasound-based investigations are being increasingly used for this purpose with variable results. AIM: To compare the diagnostic performance of resistive index (RI) and shear wave elastography (SWE) in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological results. METHODS: This is a cross-sectional and comparative study. A total of 154 kidney transplant recipients were included in this study, which was conducted at the Departments of Transplantation and Radiology, Sindh Institute of Urology and Transplan tation, Karachi, Pakistan, from August 2022 to February 2023. All consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate (GFR) after three months of transplantation were enrolled in this study. SWE and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic utility. RESULTS: The mean age of all patients was 35.32 ± 11.08 years. Among these, 126 (81.8%) were males and 28 (18.2%) were females. The mean serum creatinine in all patients was 2.86 ± 1.68 mg/dL and the mean estimated GFR was 35.38 ± 17.27 mL/min/1.73 m2. Kidney allograft biopsy results showed chronic changes in 55 (37.66%) biopsies. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SWE for the detection of chronic allograft damage were 93.10%, 96.87%%, 94.73%, and 95.87%, respectively, and the diagnostic accuracy was 95.45%. For RI, the sensitivity, specificity, PPV, and NPV were 76.92%, 83.33%, 70.17%, and 87.62%, respectively, and the diagnostic accuracy was 81.16%. CONCLUSION: The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft damage. It can be of great help during the routine follow-up of kidney transplant recipients for screening and early detection of chronic changes and selecting patients for allograft biopsy.
RESUMO
Thrombotic microangiopathy (TMA) is an uncommon but serious complication that not only affects native kidneys but also transplanted kidneys. This review is specifically focused on post-transplant TMA (PT-TMA) involving kidney transplant recipients. Its reported prevalence in the latter population varies from 0.8% to 14% with adverse impacts on both graft and patient survival. It has many causes and associations, and the list of etiologic agents and associations is growing constantly. The pathogenesis is equally varied and a variety of patho genetic pathways lead to the development of microvascular injury as the final common pathway. PT-TMA is categorized in many ways in order to facilitate its management. Ironically, more than one causes are contributory in PT-TMA and it is often difficult to pinpoint one particular cause in an individual case. Pathologically, the hallmark lesions are endothelial cell injury and intravascular thrombi affecting the microvasculature. Early diagnosis and classification of PT-TMA are imperative for optimal outcomes but are challenging for both clinicians and pathologists. The Banff classification has addressed this issue and has developed minimum diagnostic criteria for pathologic diagnosis of PT-TMA in the first phase. Management of the condition is also challenging and still largely empirical. It varies from simple maneuvers, such as plasmapheresis, drug withdrawal or modification, or dose reduction, to lifelong complement blockade, which is very expensive. A thorough understanding of the condition is imperative for an early diagnosis and quick treatment when the treatment is potentially effective. This review aims to increase the awareness of relevant stakeholders regarding this important, potentially treatable but under-recognized cause of kidney allograft dysfunction.
RESUMO
Fatty liver disease (FLD) is a highly prevalent pathological liver disorder. It has many and varied etiologies and has heterogeneous clinical course and outcome. Its proper nomenclature and classification have been problematic since its initial recognition. Traditionally, it was divided into two main categories: Alcohol-associated liver disease and nonalcoholic FLD (NAFLD). Among these, the latter condition has been plagued with nomenclature and classification issues. The two main objections to its use have been the use of negative (non-alcoholic) and stigmatizing (fatty) terms in its nomenclature. Numerous attempts were made to address these issues but none achieved universal acceptance. Just recently, NAFLD has received a new nomenclature from an international collaborative effort based on a rigorous scientific methodology. FLD has been renamed steatotic liver disease (SLD), and NAFLD as metabolic dysfunction-associated SLD. Metabolic dysfunction-associated steatohepatitis was chosen as the replacement terminology for non-alcoholic steatohepatitis. This is a significant positive change in the nomenclature and categorization of FLD and will likely have a major impact on research, diagnosis, treatment, and prognosis of the disease in the future.
RESUMO
BACKGROUND: Pregnancy in women with systemic lupus erythematosus (SLE) has remained a great challenge for clinicians in terms of maternal and fetal outcomes. The outcomes in women with pre-existing lupus nephritis (LN) are variable. The impact of different classes of LN on maternal and fetal outcomes during pregnancy is not well defined, as data is very scarce, especially from the developing countries. METHODS: A retrospective analysis was conducted on 52 women with 89 pregnancies. All had biopsy-proven LN. Those women who conceived at least 6 months after the diagnosis were included. The analysis was conducted between July 1998 and June 2018 at Sindh Institute of Urology and Transplantation (SIUT), evaluating the outcomes for both the mother and the fetus with a minimum follow-up of 12 months after child birth. RESULTS: The mean maternal age at SLE diagnosis was 21.45 ± 6 years and at first pregnancy was 26.49 ± 5.63 years. The mean disease duration was 14.02 ± 19.8 months. At conception, 47 (52.8%) women were hypertensive, 9 (10%) had active disease while 38 (42.7%) and 42 (47.2%) were in complete and partial remission, respectively. A total of 17 (19.1%) were on mycophenolate mofetil (MMF), which was switched to azathioprine (AZA). Out of 89 pregnancies, 56 (62.9%) were successful, while 33 (37.07%) had fetal complications like spontaneous abortion, stillbirth, perinatal death, and intrauterine growth retardation (IUGR). There were more vaginal deliveries (33 [58.92%]) than caesarean sections (23 [41.07%]). Renal flare was observed in 33 (37.1%) women while 15 (16.9%) developed pre-eclampsia. Proliferative LN was found in 56 (62.9%) cases, but no significant differences were found in maternal and fetal outcomes in relation to LN classes (p = .58). However, disease outcomes at 12 months were significantly poor in those with active disease at the time of conception (p < .05). There was only one maternal death. A total of 10 (11.2%) women showed deterioration in renal function and 5 (5.6%) were dialysis-dependent at 12 months. CONCLUSION: The maternal and fetal outcomes in pre-existing LN depend on the disease activity at the time of conception. No correlation was found between International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes of LN and adverse disease and pregnancy outcomes.
Assuntos
Nefrite Lúpica , Complicações na Gravidez , Resultado da Gravidez , Humanos , Feminino , Gravidez , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/complicações , Adulto , Estudos Retrospectivos , Paquistão/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto Jovem , Países em Desenvolvimento , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Azatioprina/uso terapêutico , Ácido Micofenólico/uso terapêutico , Adolescente , Recém-NascidoRESUMO
BACKGROUND: The Columbia classification identified five histological variants of focal segmental glomerulosclerosis (FSGS). The prognostic significance of these variants remains controversial. AIM: To evaluate the relative frequency, clinicopathologic characteristics, and medium-term outcomes of FSGS variants at a single center in Pakistan. METHODS: This retrospective study was conducted at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan on all consecutive adults (≥ 16 years) with biopsy-proven primary FSGS from January 1995 to December 2017. Studied subjects were treated with steroids as a first-line therapy. The response rates, doubling of serum creatinine, and kidney failure (KF) with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis, and Chi-square tests as appropriate. Data were analyzed by SPSS version 22.0. P-value ≤ 0.05 was considered significant. RESULTS: A total of 401 patients were diagnosed with primary FSGS during the study period. Among these, 352 (87.7%) had a designated histological variant. The not otherwise specified (NOS) variant was the commonest, being found in 185 (53.9%) patients, followed by the tip variant in 100 (29.1%) patients. Collapsing (COL), cellular (CEL), and perihilar (PHI) variants were seen in 58 (16.9%), 6 (1.5%), and 3 (0.7%) patients, respectively. CEL and PHI variants were excluded from further analysis due to small patient numbers. The mean follow-up period was 36.5 ± 29.2 months. Regarding response rates of variants, patients with TIP lesions achieved remission more frequently (59.5%) than patients with NOS (41.8%) and COL (24.52%) variants (P < 0.001). The hazard ratio of complete response among patients with the COL variant was 0.163 [95% confidence interval (CI): 0.039-0.67] as compared to patients with NOS. The TIP variant showed a hazard ratio of 2.5 (95%CI: 1.61-3.89) for complete remission compared to the NOS variant. Overall, progressive KF was observed more frequently in patients with the COL variant, 43.4% (P < 0.001). Among these, 24.53% of patients required kidney replacement therapy (P < 0.001). The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57 (95%CI: 1.87-113.49) as compared to patients with the TIP variant. CONCLUSION: In conclusion, histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.
RESUMO
Tumor deposits (TDs) are defined as discrete, irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor, and are usually found in the lymphatic drainage area of the primary tumor. By definition, no residual lymph node structure should be identified in these tumor masses. At present, TDs are mainly reported in colorectal cancer, with a few reports in gastric cancer. There are very few reports on breast cancer (BC). For TDs, current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor tissue. Even some pathologists classify a TD as two lymph node metastases for calculation. Some pathologists also believe that TDs belong to the category of disseminated metastasis. Therefore, regardless of the origin, TDs are an indicator of poor prognosis. Moreover, for BC, sentinel lymph node biopsy is generally used at present. Whether radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still inconclusive. The present commentary of this clinical issue has certain guiding significance. It is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.
RESUMO
Null.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , ConsensoRESUMO
The second half of the previous century witnessed a tremendous rise in the number of clinical kidney transplants worldwide. This activity was, however, accompanied by many issues and challenges. An accurate diagnosis and appropriate management of causes of graft dysfunction were and still are, a big challenge. Kidney allograft biopsy played a vital role in addressing the above challenge. However, its interpretation was not standardized for many years until, in 1991, the Banff process was started to fill this void. Thereafter, regular Banff meetings took place every 2 years for the past 30 years. Marked changes have taken place in the interpretation of kidney allograft biopsies, diagnosis, and classification of rejection and other non-rejection pathologies from the original Banff 93 classification. This review attempts to summarize those changes for increasing the awareness and understanding of kidney allograft pathology through the eyes of the Banff process. It will interest the transplant surgeons, physicians, pathologists, and allied professionals associated with the care of kidney transplant patients.
RESUMO
Currently, the most feasible and widely practiced option for patients with end-stage organ failure is the transplantation of part of or whole organs, either from deceased or living donors. However, organ shortage has posed and is still posing a big challenge in this field. Newer options being explored are xenografts and engineered/bioengineered tissues/organs. Already small steps have been taken in this direction and sooner or later, these will become a norm in this field. However, these developments will pose different challenges for the diagnosis and management of problems as compared with traditional allografts. The approach to pathologic diagnosis of dysfunction in these settings will likely be significantly different. Thus, there is a need to increase awareness and prepare transplant diagnosticians to meet this future challenge in the field of xenotransplantation/ regenerative medicine. This review will focus on the current status of transplant pathology and how it will be changed in the future with the emerging scenario of routine xenotransplantation.
RESUMO
INTRODUCTION/AIM: The Luminex assay, where beads are coated with a single HLA antigen, has been shown to detect HLA antibodies with more sensitivity and specificity as compared to microlymphocytotoxicity (CDC) assay and flow cross match (FCXM). We report the impact of low Mean Flourescence intensity (MFI) pre-transplant DSA by Luminex with negative CDC and FCXM on acute rejection, graft function, and survival. METHODS: In this retrospective study between January 2015 to December 2021, 45 recipients had pre-transplant anti-HLA donor-specific antibodies (DSAs) detected by Luminex. Two control groups of 45 patients each matched for age and gender, first with non-DSA HLA antibodies and second with no antibodies by Luminex were selected to compare outcomes with DSA group. RESULTS: In the DSA group of 45, 22 (48.8%) had class I (MFI mean 4043 ± 1909, range: 1096-7111), 20 (44.4%) class II (MFI mean 3601 ± 2310, range: 1031-9259), and 3 (6.6%) both class I (MFI mean 4746 ± 1922) and class II (MFI mean 3940 ± 2312) antibodies. Acute rejection episodes were reported in 15.6%, DSA group, 17.8% in non-DSA, and 24.4% in no antibody group (p = .538). Death censored graft survival at 1 and 5 years was 98% and 93% in DSA group, 100% and 95% in non-DSA and 93% and 85% in the no antibody group (p = .254). CONCLUSIONS: Patients with low MFI DSA pre-transplant, with a negative CDC and FCXM under ATG induction, have similar graft outcomes at 1 and 5 years when compared to non-DSA and no antibody groups.
Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Anticorpos , Doadores de Tecidos , Transplantados , Soro Antilinfocitário , Sobrevivência de Enxerto , Rejeição de Enxerto/etiologia , Antígenos HLA , Teste de Histocompatibilidade , IsoanticorposRESUMO
BACKGROUND: Proteinuria is an important and well-known biomarker of many forms of kidney injury. Its quantitation is of particular importance in the diagnosis and management of glomerular diseases. Its quantification can be done by several methods. Among these, the measurement of 24-h urinary protein excretion is the gold standard method. However, it is cumbersome, time-consuming, and inconvenient for patients and is not completely foolproof. Many alternative methods have been tested over time albeit with conflicting results. Among the latter, the measurement of urine protein-to-creatinine ratio (uPCR) in single-voided urinary samples is widely used. The majority of studies found a good correlation between uPCR in single urine samples with 24-h urinary protein estimation, whereas others did not. AIM: To investigate the correlation of spot uPCR with 24-h urinary protein estimation in patients suffering from different forms of glomerulopathies at a single large-volume nephrological center in Pakistan. METHODS: This cross-sectional, observational study was conducted at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan from September 2017 to March 2018. All newly presenting adult patients with proteinuria who were being investigated for suspected glomerulonephritis and persistent proteinuria with ages between 18 to 60 years were enrolled. All patients were given detailed advice regarding 24-h urine collection starting at 7:00 AM for total protein and creatinine excretion estimations. A spot urine sample was collected the next day at the time of submission of a 24-h urine sample for measuring uPCR along with a blood sample. The data of patients were collected in a proforma. SPSS version 20.0 was used for statistical analysis. RESULTS: A total of 157 patients were included. Their mean age was 30.45 ± 12.11 years. There were 94 (59.8%) males and 63 (40.2%) females. The mean 24-h urinary protein excretion was 3192.78 ± 1959.79 mg and the mean spot uPCR was 3.16 ± 1.52 in all patients. A weak but significant correlation was observed between spot uPCR and 24-h urinary protein excretion (r = 0.342, P = 0.01) among all patients. On subgroup analysis, a slightly better correlation was found in patients older than 47 years (r = 0.78), and those with body mass index > 25 kg/m2 (r = 0.45). The Bland and Altman's plot analysis comparing the differences between spot uPCR and 24-h protein measurement also showed a wide range of the limits of agreement between the two methods. CONCLUSION: Overall, the results from this study showed a significant and weakly positive correlation between spot uPCR and 24-h urinary protein estimation in different forms of glomerulopathies. The agreement between the two methods was also poor. Hence, there is a need for careful interpretation of the ratio in an unselected group of patients with kidney disease.
RESUMO
The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has become a global challenge of unprecedented nature since December 2019. Although most patients with COVID-19 exhibit mild clinical manifestations and upper respiratory tract involvement, in approximately 5%-10% of patients, the disease is severe and involves multiple organs, leading to multi-organ dysfunction and failure. The liver and gastrointestinal tract are also frequently involved in COVID-19. In the context of liver involvement in patients with COVID-19, many key aspects need to be addressed in both native and transplanted organs. This review focuses on the clinical presentations and laboratory abnormalities of liver function tests in patients with COVID-19 with no prior liver disease, patients with pre-existing liver diseases and liver transplant recipients. A brief overview of the history of COVID-19 and etiopathogenesis of the liver injury will also be described as a prelude to better understanding the above aspects.
RESUMO
A 50-year male presented with vomiting and dysphagia for 2 weeks. Laboratory workup showed a positive serology for hepatitis C and normal serum α-fetoprotein (AFP) levels. CT abdomen revealed a large lesion in the right lobe of the liver extending upto the lower esophagus causing significant luminal narrowing and dysphagia. The enhancement pattern on the CT scan was not consistent with hepatocellular carcinoma. Liver lesion biopsy showed an infiltrating spindle cell lesion exhibiting fascicles of spindle cells with moderately hyperchromatic nuclei and perinuclear vacuolization. Mitotic count was 2-3/10 HPFs. Immunohistochemical markers were positive for CK AE1/AE3 and vimentin. Thus, a diagnosis of sarcomatoid carcinoma was made on the basis of morphological and immunohistochemical features. Due to unresectable disease and poor functional status, palliative care was opted for. Key Words: Dysphagia, Vomiting, Liver biopsy, Sarcomatoid carcinoma.
Assuntos
Carcinoma Hepatocelular , Transtornos de Deglutição , Neoplasias Hepáticas , Sarcoma , Neoplasias de Tecidos Moles , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Transtornos de Deglutição/etiologia , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Sarcoma/patologia , Vimentina , Vômito , alfa-FetoproteínasRESUMO
INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is one of the common causes of end-stage kidney disease (ESKD) in adults with primary glomerular diseases. Information on clinical course and long-term renal outcome of primary FSGS in adults are scanty. We aimed to determine the clinical course and long-term outcome of primary FSGS in a large number of adult patients from a tertiary care kidney center in Pakistan. METHODS: A retrospective review of the clinical charts of all adults (≥ 16 years) with a biopsy proven diagnosis of FSGS presenting to Sindh Institute of Urology and Transplantation, Karachi, between January 1995 and December 2017 was carried out. Cases with secondary FSGS were excluded. Relevant data items were retrieved both at baseline and on last follow-up. RESULTS: Among 401 adults with primary FSGS, 144 (35.9%) were followed for a mean duration of 66.6 ± 27.4 months, out of which, 129 (89.5%) were treated with steroids and immunosuppressants. Response to steroids was obtained in 62 (48%) patients, while 67 (52%) showed no response. Among responders, 24/62 (38.7%) relapsed after a mean duration of 24.2 ± 23.2 weeks, who were re-treated with same dose of steroids alone or combined with cyclosporine and all achieved remission. The long-term outcomes were significantly different between steroid responsive and nonresponsive cohorts. None of the patients in steroid responsive group developed ESKD or died, while 7 (10.4%) patients in nonresponsive group developed ESKD and 2 (3%) died. CONCLUSION: Almost half of adults with primary FSGS achieved sustained remission with steroids and immunosuppressants and consequently exhibited excellent long-term outcome. DOI: 10.52547/ijkd.6815.