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.
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.
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.
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.
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.
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.
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.
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.
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Retrospective Studies , Antibodies , Tissue Donors , Transplant Recipients , Antilymphocyte Serum , Graft Survival , Graft Rejection/etiology , HLA Antigens , Histocompatibility Testing , Isoantibodies
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.
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.
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.
Carcinoma, Hepatocellular , Deglutition Disorders , Liver Neoplasms , Sarcoma , Soft Tissue Neoplasms , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/diagnosis , Deglutition Disorders/etiology , Humans , Liver Neoplasms/complications , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Male , Sarcoma/pathology , Vimentin , Vomiting , alpha-Fetoproteins
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.
Glomerulosclerosis, Focal Segmental , Kidney Failure, Chronic , Adult , Cyclosporine/therapeutic use , Glomerulosclerosis, Focal Segmental/complications , Glomerulosclerosis, Focal Segmental/diagnosis , Glomerulosclerosis, Focal Segmental/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/complications , Retrospective Studies , Steroids/therapeutic use , Treatment Outcome
Chronic hepatitis C virus (HCV) infection is a major global public health problem, particularly in developing part of the world. Significant advances have been made in the early diagnosis and treatment of the disease. Its management has been particularly revolutionized during the past two decades. In this review, we summarize the major advances in the diagnostic and management armamentarium for chronic HCV infection. The focus of the present review is on the newer directly acting anti-viral agents, which have revolutionized the management of chronic HCV infection. Management of uncomplicated chronic HCV infection and of specific complications and special at-risk populations of patients will be covered in detail. Despite the advent and approval of highly effective and well tolerable oral agents, still many challenges remain, particularly the affordability, the equitable distribution and access to later drugs. The World Health Organization aims to eliminate viral hepatitis including HCV by 2030 since its poses a major public health threat. There is an urgent need to ensure uniform and early access to diagnostic and therapeutic facilities throughout the world if the later goal has to be realized.
Renal diseases are one of the common causes of morbidity and mortality in elderly population. Currently, the spectrum of renal diseases in elderly population in our country is unknown. The aim of this study was to determine the pattern of renal diseases in elderly patients in Pakistan. In this retrospective, observational study, we included all consecutive patients aged ≥60 years, on whom native renal biopsies were performed during a period of 25 years from January 1994 to December 2018. The final histologic diagnosis was categorized into four groups, primary glomerular diseases (PGDs), secondary glomerular diseases (SGDs), tubulointerstitial disease (TID), and vascular diseases (VDs). A total of 324 renal biopsies are performed in the study period. The mean age was 64.6 ± 5.1 years, range of 60-80 years with a male-to-female ratio of 3.26:1. The mean serum creatinine at biopsy was 4.1 ± 2.86 mg/dL. Indications for biopsy were acute kidney injury (AKI) in 141 (43.5%), followed by nephrotic syndrome (NS) in 128 (39.5%). Renal disease category was PGD in 204 (63%), SGD in 42 (13%), TID in 58 (17.9%), and VD in 20 (6.1%). Focal segmental glomerulosclerosis (FSGS) is the leading cause of PGD in 55 (27%). Among SGD, amyloidosis was the most common cause in 27 (64.3%). In patients who were biopsied for AKI, majority were crescentic glomerulonephritis accounting for 28 (19.8%). In conclusion, AKI and NS are the common biopsy indications in our population. Overall FSGS is the most common histologic diagnosis in this cohort.
Acute Kidney Injury , Glomerulosclerosis, Focal Segmental , Kidney Diseases , Nephritis, Interstitial , Nephrotic Syndrome , Humans , Aged , Male , Female , Middle Aged , Aged, 80 and over , Glomerulosclerosis, Focal Segmental/pathology , Retrospective Studies , Developing Countries , Kidney Diseases/diagnosis , Kidney Diseases/epidemiology , Kidney Diseases/pathology , Kidney/pathology , Nephrotic Syndrome/epidemiology , Nephritis, Interstitial/diagnosis , Acute Kidney Injury/pathology , Biopsy
To share our experience of establishing a bone bank in Pakistan, and the clinical use of these indigenously produced bone grafts. We retrospectively reviewed our experience of the procurement, processing, and storage of bone grafts at a bone bank in Karachi, Pakistan, the first bone bank to be established in a public sector hospital in Pakistan. The bone bank was established at Sindh Institute of Urology and Transplantation (SIUT), Karachi, in collaboration with Department of Orthopaedic Surgery, Dow University of Health Sciences/Civil Hospital, Karachi (CHK) in May, 2015. Since then, a large number of bone grafts from the tissue bank have been used for various orthopedic procedures. This paper describes the problems and challenges faced in establishing and running a tissue bank in a Muslim and a developing country and the progress of the bone bank over the first 4 years. A total of 93 bone grafts were retrieved and preserved in the bone bank over the 4-year period. Among these, 56 (60.2%) bones were retrieved from male donors and 37 (39.8%) from females. The mean age of all donors was 55.9 ± 15.34 years (range: 16-90 years). All bone donors were living patients. No c bones were obtained from deceased donors. Types of bone grafts included: femoral heads, 68; head with neck of femur, 19; radius and ulna, 1; lower femur, knee joint, lower leg and foot bones, 4; and skull bone, 1. All grafts were subjected to aerobic and anaerobic bacterial cultures, as well as fungal cultures. Microbiological contamination was observed in 18/93 (19.35%). All culture positive bones were discarded. Bone grafts issued from the bank and transplanted were 51/93 (54.8%) in all. Bone grafts were used in a variety of tumor and non-tumor orthopaedic procedures in CHK. Nine bone grafts were donated to the other hospitals to be used for revision total hip replacement and tumor surgeries. There were no service charges. Two patients (3.92%) developed infections postoperatively, one superficial and one deep. No other complications were noted. This is the preliminary report on the establishment and functioning of a bone bank in a public sector hospital in Pakistan. The favorable outcome has inculcated confidence in orthopedic surgeons for greater use of bone allografts for a variety of indications in this country.
Bone Banks , Adolescent , Adult , Aged , Aged, 80 and over , Allografts , Bone Transplantation , Female , Femur Head , Humans , Male , Middle Aged , Pakistan , Retrospective Studies , Young Adult
