Warfarin-related Nephropathy.

Warfarin-related nephropathy also referred to as anticoagulant-related nephropathy (ACRN) is a type of acute kidney injury (AKI) that may be caused by excessive anticoagulation with warfarin and other anticoagulants. Despite the well-described histological entity, the clinical course and approach to ACRN in patients requiring life-long anticoagulation are however not well described in the literature. We report a 50-year-old Indian woman who was on prolonged anticoagulant therapy post-mitral valve replacement. She presented with AKI, and renal biopsy was suggestive of ACRN. Steroids were given and her creatinine levels reached within the normal range in 2 weeks. A presumptive diagnosis of ACRN should be made if a severe warfarin coagulopathy is present and if other causes of AKI have been excluded, in patients with chronic anticoagulant therapy. Renal function should be monitored regularly in patients who are on anticoagulant therapy.

Monoclonal Gammopathy of Renal Significance Presenting as Cryoglobulinemic Glomerulonephritis: A Case Report and Review of Literature.

Monoclonal gammopathy of renal significance (MGRS) can present with myriad of morphological features. We report a case of MGRS in a 46-year-old man who presented with nephrotic-range proteinuria and renal insufficiency. Renal biopsy showed amorphous eosinophilic periodic acid-Schiff positive deposits in capillary loops and lamda light chain positivity on immunofluorescence, suggestive of cyoglobulinemic glomerulonephritis. Serum cryoglobulins were positive. Serum immunoelectrophoresis and immunofixation showed a M band of 0.5 g/dl of IgG lambda type. Bone marrow showed 8% of plasma cells which confirmed the diagnosis of MGRS.

Immunohistochemical Analysis of Anti-phospholipase A2 Receptor Antibody on Renal Biopsies: A Single Tertiary Care Center Study.

Membranous nephropathy (MN) is one of the common cause of nephrotic syndrome. The discrimination between primary MN (iMN) and secondary MN is essential because of treatment implications. Immunohistochemical (IHC) evaluation with the help of anti-phospholipase A2 receptor (PLA2R) antibody helps in tissue evaluation of iMN, which is an easy, cost-effective, and pathologist-friendly technique. The study included 82 cases of MN over a period of 3 years. IHC using PLA2R antibody was performed on iMN and secondary cases with adequate tissue. Cases of minimal change disease (MCD) were included as control. Granular staining along the basement membrane in the absence of staining of podocytes was considered positive. Medical records were verified for clinical information, baseline biochemical parameters, details of viral markers, connective tissue disease profile, and basic imaging workup. Of the 82 cases of MN, 51 were iMN and 31 secondary MN (sMN). Thirteen MCD cases were included as control. IHC with PLA2R antibody showed a sensitivity of 91.8% and specificity of 95.1%, positive predictive value of 95.7%, and negative predictive value of 90.7% in the diagnosis of iMN. The other parameters, either clinical or laboratory, did not show significant differences between iMN and sMN groups. The results of PLA2R staining by IHC were comparable with other studies and showed a higher sensitivity (91.8%) and specificity (95.1%). IHC with anti-PLA2R antibody can be considered as the standard diagnostic approach to identify iMN and offer scope for individualized treatment.

Acute Ciprofloxacin-Induced Crystal Nephropathy with Granulomatous Interstitial Nephritis.

Crystal-induced acute kidney injury (AKI) is caused by the intratubular precipitation of crystals, which results in obstruction and kidney injury. Ciprofloxacin, a commonly used antibiotic, causes AKI secondary to immune-mediated interstitial injury. Rare mechanisms of ciprofloxacin-induced renal injury include crystalluria, rhabdomyolysis, and granulomatous interstitial nephritis. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy due to ciprofloxacin occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of ciprofloxacin-induced crystal nephropathy and granulomatous interstitial nephritis in a young patient with no other predisposing factors. The patient responded to conservative treatment without the need for glucocorticoids.

Acyclovir-induced thrombotic microangiopathy.

Acyclovir is a commonly used antiviral drug. Acute kidney injury (AKI) due to intratubular crystal precipitation and interstitial nephritis is well known. Here we present a case of acyclovir induced AKI in a 61 year old male with herpes zoster, which presented like thrombotic microangiopathy with acute interstitial nephritis. This is the first case report on acyclovir causing thrombotic microaniopathy with partial improvement in renal function after plasmapharesis.

Unusual cause of glomerular deposition disease: Collagenofibrotic glomerulopathy.

Collagenofibrotic glomerulopathy is a rare condition characterized by deposition of Type III collagen fibers in the subendothelial space and mesangium of the glomerulus. Only 17 cases have been reported from India. A definite diagnosis can only be established when typical histological findings are supported by electron microscopy. It is characterized by indolent progression and has no definitive therapy.

Rituximab in the treatment of refractory late acute antibody-mediated rejection: Our initial experience.

Antibody-mediated rejection (AMR) is not uncommon after renal transplantation and is harder to handle compared to cell-mediated rejection. When refractory to conventional therapies, rituximab is an attractive option. This study aims to examine the effectiveness of rituximab in refractory late acute AMR. This is a retrospective study involving nine renal transplant recipients. Four doses of rituximab were administered at weekly interval for 4 weeks, at a dose of 375 mg/m2. The mean age of patients was 35.3 ± 7.38 years. The median period between transplantation and graft dysfunction was 30 ± 20 months. Mean serum creatinine at the time of discharge after transplantation and at the time of acute AMR diagnosis was 1.14 ± 0.19 mg/dl and 2.26 ± 0.57 mg/dl, respectively. After standard therapy, it was 2.68 ± 0.62 mg/dl. One patient died of Pseudomonas sepsis and three patients progressed to end-stage renal disease (ESRD). Four biopsies showed significant plasma cell infiltrations. Mean serum creatinine among non-ESRD patients at the end of 1 year progressed from 2.3 ± 0.4 to 3.8 ± 1.2 mg/dl (P value 0.04). eGFR prior to therapy and at the end of 1 year were 34.4 ± 6.18 and 20.8 ± 7.69 ml/min (P value 0.04), respectively. Only one patient showed improvement in graft function in whom donor-specific antibody (DSA) titers showed significant improvement. Rituximab may not be effective in late acute AMR unlike in early acute AMR. Monitoring of DSA has a prognostic role in these patients and plasma cell rich rejection is associated with poor prognosis.

Expanding the antibody-mediated component of plasma cell-rich acute rejection: A case series.

Renal allograft rejection is mediated by T-cells (T-cell mediated rejection) or by donor-specific antibodies (DSAs) (antibody mediated rejection, ABMR). Plasma cell-rich acute rejection (PCAR) is a unique entity due to its peculiar morphology and poor prognostic behavior. All allograft biopsies done at our center from January 2013 to October 2014 were reviewed, and seven were identified with a diagnosis of PCAR with antibody mediated rejection (ABMR). The allograft biopsies were classified as per the Banff 2007 schema. Immunohistochemistry with C4d, SV 40, CD3, CD20, CD138, kappa and lambda light chain was performed. Total 210 allograft biopsies were performed in the study period of which seven biopsies (3.3%) were diagnosed as PCAR with ABMR. All these were late ABMRs (more than 6 months) with median posttransplant duration of 17 months. The allograft biopsy showed features of PCAR along with glomerulitis, peritubular capillaritis, and positive C4d. DSA was positive in six patients. All the patients were treated with standard therapeutic measures of acute cellular rejection (ACR) and ABMR including steroids, plasma exchange, rituximab and intravenous immunoglobulins. All the patients had persistent graft dysfunction or graft loss on follow-up.

Idiopathic nodular glomerulosclerosis: Report of two cases and review of literature.

Nodular glomerulosclerosis, a pathological finding characterized by areas of marked mesangial expansion with accentuated glomerular nodularity can be seen in a number of conditions including diabetic nephropathy, amyloidosis, light chain deposition disease, fibrillary and immunotactoid glomerulopathy, collagen type III disease, nodular membranoproliferative glomerulonephritis, and Takayasu's arteritis. Idiopathic nodular glomerulosclerosis is a diagnosis of exclusion and is reported in patients with hypertension, smoking, chronic obstructive pulmonary disease, obesity, metabolic syndrome, etc. We report two cases of idiopathic nodular glomerulosclerosis, one in obese hypertensive male and the other in nonhypertensive, nonobese female patient.

Pediatric meningiomas an aggressive subset: a clinicopathological and immunohistochemical study.

BACKGROUND: Meningiomas are uncommon neoplasms in the pediatric age group and differ in various aspects from their adult counterparts. They account for 0.4-4.6% of all primary brain tumors. AIMS: To retrospectively analyze the clinicopathological and immunohistochemical features of pediatric meningiomas. MATERIALS AND METHODS: Meningiomas in patients under 18 years of age diagnosed between January 2001 to December 2011 were analyzed retrospectively. The hematoxylin and eosin stained sections and Ki 67 labelling index (LI) were reviewed for all the cases Results: The pediatric meningiomas accounted for 1.52% of total meningiomas (15/983). The mean age at presentation was 12 years with male to female ratio of 1.5:1. The presenting symptoms were headache, seizures, and motor deficits. The histology included 9 cases (60%) of atypical meningioma (WHO grade II) followed by 4 cases (26.67%) of WHO grade-I and 2 cases (13.33%) of anaplastic meningioma (WHO grade III). Five cases had a recurrence. Ki67 LI ranged from 0.5% to 1.5% in grade I, 0.5% to 15% in grade II and 13% to 24% in grade III meningiomas. CONCLUSION: Meningiomas are rare in children and show a male preponderance. There was a higher incidence of atypical and anaplastic meningiomas in pediatric population.

Primary intramedullary non-Hodgkin's lymphoma in an immunocompetent child.

STUDY DESIGN: Case report. OBJECTIVES: Primary intramedullary spinal cord lymphoma is a rare entity. Studies have shown that there is a recent increase in the number of patients regardless of the status of the immunity. High index of suspicion should be kept in all patients with intramedullary tumors. Multidisciplinary approach at the earliest is required for best outcomes. SETTING: Department of Neurosurgery, Medical Oncology, Pathology and Radiation oncology. Nizam's Institute of Medical Sciences, Hyderabad, India. METHODS: We describe the case of an 11-year-old boy who presented with paraparesis and sensory loss below T10 level. On imaging, the dorsal spine showed intramedullary lesion mimicking an astrocytoma. RESULTS: Surgical decompression of the tumor was done and histopathology showed non-Hodgkin's lymphoma, diffuse large B-cell type. There were no findings suggestive of congenital or acquired immunodeficiency. After complete staging evaluation, we instituted chemotherapy with modified DeAngelis protocol. At 2 years post treatment, he is in complete remission with near normal neurological status. CONCLUSIONS: Intramedullary spinal cord diffuse B-cell lymphoma in a pediatric age group is very rare and hence requires a high index of suspicion in patients presented with myelopathy. The outcomes are encouraging with current multidisciplinary approach.

Spectrum of malignancies in human immunodeficiency virus - positive patients at a Tertiary Care Centre in South India.

CONTEXT: India has a very large number of patients living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Opportunistic infections in these patients are commonly encountered. However, malignancies in such patients also do occur. AIM: The aim was to study the spectrum of malignancies in HIV-positive patients at a tertiary health care center. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS: The cases were retrieved from pathology record files at our Institute from January 2003 to December 2008. The follow-up was obtained from Medical oncology records. The morphology of each case was reviewed along with immunohistochemistry wherever done. RESULTS: There were 61 such cases (51 males, 10 females). The age range was 7-78 years with a median of 35 years. The clinical presentation varied according to the malignancy. The largest group was non-Hodgkin lymphoma (18 nodal, 23 extra-nodal). The others included carcinoma breast (4), chronic myeloid leukemia (3), Burkitt Leukemia (2), squamous cell carcinoma anal region (2), multiple myeloma (2) and one each of miscellaneous malignancies (7). CONCLUSION: Malignancies in HIV positive individual occurred in younger individuals. Non-Hodgkin lymphomas, especially extra-nodal lymphomas, were the most common malignancy. There were no cases of proven Kaposi's sarcoma or invasive cervical carcinomas. There were two cases of multiple myeloma which are infrequently reported.

Granulomatous interstitial nephritis: Our experience of 14 patients.

Granulomatous interstitial nephritis (GIN) is a rare condition. Drugs, infections, immune processes, and foreign body reaction are the main causes. We identified a total of 14 patients with GIN during a period of 13 years in 2798 renal biopsies. There were 8 males and 6 females in the age range of 20-70 (mean 35 ± 12) years. The serum creatinine at presentation was 6.7 ± 3.8 (range: 2.3-14.7) mg/dl. In nine patients tuberculosis was the causative agent. Drugs (n = 2) and Wegener's granulomatosis (n = 1) were other etiologies. Systemic lupus erythematosis (SLE) and Immunoglobulin A nephropathy (IgAN) were seen in one patient each. Patients with tuberculosis were treated with antituberculous therapy and three of them improved. Four out of six patients who required dialysis at presentation remained dialysis dependent, one of whom underwent renal transplantation. Two patients progressed to end stage renal disease after 7 years and 9 years each. The patients with drug induced GIN had improvement in renal function after prednisolone treatment. Patients with SLE, and Wegener's granulomatosis responded to immunosuppression. Patient with IgAN was on conservative management. Finally, six patients were on conservative management for chronic renal failure.

Correlation of p53 and KI-67 expression with grade and subtype of ependymoma.

INTRODUCTION: The morphological criteria for grading ependymomas were always felt subjective. Recently some studies have showed that Ki-67 and p53 immunolabeling are important prognostic markers in ependymomas. MATERIALS AND METHODS: All the cases of ependymomas diagnosed from 2005 to 2010 were graded according to WHO classification for central nervous system (CNS) tumors 2007. Two tissue microarray (TMA) blocks were prepared. Immunohistochemical analysis with glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), Ki-67 and p53 was performed. The difference in expression of p53 and Ki-67 in various tumor grades and subtypes was evaluated using Student's t test. RESULTS: There were 54 cases with a M: F ratio of 1.34 : 1, age ranging from 7 years to 65 years (mean 29.35 years). There were 33 intracranial and 21 spinal cases. There were 9 grade I ependymomas, 32 grade II ependymomas and 13 grade III ependymomas. GFAP immunopositivity was seen in all the cases and EMA was positive in 49% cases. The mean p53 indices were higher in grade III and grade II tumors (26.26% and 26.08%) as compared to subependymomas (7.25%). But these values did not show statistical significance (P = 0.2). The Ki-67 labeling index increased from grade I to grade III tumors. The difference was highly significant between grade II and grade III (0.5% vs. 2.75, P = 0.016). CONCLUSION: Ki-67 labeling index correlates with grade of ependymoma (P = 0.016). There is no correlation between p53 expression and grade of ependymomas.

Nondiabetic kidney disease in type 2 diabetic patients: A single center experience.

Nondiabetic renal disease (NDRD) is seen as a cause of proteinuria and renal failure in type 2 diabetes mellitus (DM). The clinical differences between NDRD and diabetic glomerulosclerosis (DGS) are not clear. This study was done to find the spectrum of NDRD in type 2 DM patients and differences in clinical profile between NDRD and DGS patients. Data of patients with type 2 DM who underwent renal biopsy in this institute from 1990 to 2008 were analyzed retrospectively. Patients were categorized as isolated NDRD, NDRD with DGS, and isolated DGS. A total of 75 patients were included. Mean age was 45 ± 10.2 years, male to female ratio was 3.1 : 1, median duration of DM was 12 months (range, 1 year-15 years), proteinuria was 4.2 ± 3.4 g/day, and serum creatinine was 4.3 ± 3.9 mg/dl. Hypertension was observed in 63 (84%) cases and microscopic hematuria in 24 (32%) cases. Nephrotic syndrome (38.7%) was the commonest clinical presentation. Forty-eight (64%) cases had NDRD and 27 (36%) had DGS. The commonest NDRD was minimal change disease (12.5%). Three (6.3%) patients had lupus nephritis. Tubulointerstitial nephritis has been observed in 10.4% patients. No significant differences between NDRD and DGS patients were found except hypertension which was significantly high in the DGS group. Acute kidney injury and nephritic syndrome were not observed in the DGS group. In conclusion, the incidence of biopsy-proven NDRD in type 2 DM in this study was high. Kidney biopsy aided in the detection of NDRD in clinically suspected patients.