IgM nephropathy presenting as full blown crescentic glomerulonephritis: first report in the literature

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Frequency and clinicopathological correlations of histopathological variants of idiopathic focal segmental glomerulosclerosis in nephrotic adolescents.

OBJECTIVE: To determine the frequency and clinicopathological correlations of focal segmental glomerulosclerosis variants in adolescents with idiopathic nephrotic syndrome. METHODS: All consecutive adolescents (12 to 18 years) who presented with idiopathic nephrotic syndrome in the period, January 2009 to December 2012, and in whom the histological diagnosis of focal segmental glomerulosclerosis was made on renal biopsies, were included in this prospective study. Their clinical, laboratory and histopathological features at the time of presentation or biopsy were noted from the case files and the biopsy reports. RESULTS: Among 50 adolescents, 34 (68%) were males and 16 (32%) females.The mean age was 15.14 +/- 2.3 years. The mean duration of disease was 6.3 +/- 11.2 months.The mean serum creatinine was 0.96 +/- 0.82 mg/dl. The mean 24-hour urinary protein excretion was 3.8 +/- 0.68 grams. Biopsy indications were steroid-resistant nephritic syndrome in 15 (30%), steroid-dependant nephritic syndrome in 19 (38%) and adolescent nephritic syndrome in 16 (32%) cases. Among the focal segmental glomerulosclerosis variants, 40 (80%) were "not otherwise specified", followed by the collapsing variant, which accounted for 8 (16%) cases. The tip and cellular variants, both were found in one (2%) case each. Among the histological features, global glomerulosclerosis was found in 23 (46%) cases, and segmental scarring/collapse in all (100%). A variable degree of tubular atrophy and interstitial fibrosis was noted in 44 (88%) cases. CONCLUSION: The results from this study indicate that the pattern of focal segmental glomerulosclerosis variants differs markedly in adolescents compared with younger children.

Acute renal failure in a young female with vaginal bleeding with partial recovery.

Implication for health policy/practice/research/medical education: Glomerular collapse is one of the morphological patterns of response of kidney parenchyma to a variety of noxious agents. As such, it is commonly observed on renal biopsies showing a variety of diseases. It is important to report this lesion in the context of underlying major pathology so as not to confuse it with idiopathic collapsing glomerulopathy. The prognosis of this lesion is determined in such cases by the underlying pathology.

Prevalence and risk factors for early chronic allograft nephropathy in a live related renal transplant program.

BACKGROUND: Chronic allograft nephropathy (CAN) is a common cause of delayed allograft failure throughout the world. Its prevalence and risk factors vary depending on a number of factors. There is little information on the prevalence and risk factors for early CAN in live related renal transplant patients. OBJECTIVES: We aimed to determine the prevalence and the risk factors of early CAN in our setup. PATIENTS AND METHODS: The study was conducted at Sindh Institute of Urology & Transplantation (SIUT), Karachi, from 2002 to 2005 on patients who had live related kidney transplantation and underwent at least one allograft biopsy within 18 months of transplantation. The biopsies were performed and prepared in accordance with established indications and guidelines. The Banff 97 classification and its updates were used to diagnose and categorize the biopsy pathology. Patients were divided into two groups depending on the presence or absence of CAN on biopsies. Following parameters were compared among the groups: age, sex, human leukocyte antigen (HLA) match, immunosuppression used, acute rejection (AR) episodes, urinary tract infections (UTIs), viral infections, cyclosporine levels, early and late graft function monitored by serum creatinine. RESULTS: A total of 164 patients fulfilled the study inclusion criteria. The mean age of recipients and donors was relatively young. The majority of the donors were siblings. The overall prevalence of CAN was 25.6% (42/164), between 3 and 18 months post transplantation. The median time to the appearance of CAN was 9 months post-transplant. The prevalence of CAN increased as post-transplant duration increased. In 39 (92.8%) subjects, CAN was detected on the second or subsequent graft biopsy. Only 3 (7.2%) patients showed CAN on the first graft biopsy. The majority of cases belonged to moderate degree or grade II CAN. The mean serum creatinine values were higher in the CAN group at the time of discharge and all times post-transplantation. CONCLUSIONS: In conclusion, the results show that serum creatinine at the time of discharge is a useful predictor of later development of chronic changes in the allograft. Further studies are needed to identify the risk factors for the early development of chronic changes in living related renal transplant program.

Oxidative DNA damage as a potential early biomarker of Helicobacter pylori associated carcinogenesis.

Helicobacter pylori infection is an established risk factor for gastritis, gastric ulcer, peptic ulcer and gastric cancer. CagA +ve H. pylori has been associated with oxidative DNA damage of gastric mucosa but their combined role in the development of gastric cancer is still unknown. Here we compare the combined expression of cagA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in normal, gastritis and gastric cancer tissues. Two hundred gastric biopsies from patients with dyspeptic symptoms, 70 gastric cancer tissue samples and 30 gastric biopsies from non-dyspeptic individuals (controls) were included in this study and 8-OHdG was detected by immunohistochemistry (IHC). Histological features and the presence of H. pylori infection were demonstrated by Hematoxylin and Eosin (HE), Giemsa and alcian blue-periodic acid-Schiff ± diastase (AB-PAS ± D) staining. DNA was extracted from tissues and polymerase chain reaction (PCR) performed to determine the presence of ureaseA and cagA genes of H. pylori. The results showed the presence of H. pylori in 106 (53 %) gastric biopsies out of 200 dyspeptic patients, including 70 (66 %) cases of cagA + ve H. pylori. The presence of cagA gene and high expression of 8-OHdG was highly correlated with severe gastric inflammation and gastric cancer particularly, in cases with infiltration of chronic inflammatory cells (36.8 % cagA + ve, 18 %), neutrophilic activity (47.2 %, 25.5 %), intestinal metaplasia (77.7 %, 35.7 %) and intestinal type gastric cancer (95 %, 95.4 %) (p ≤ 0.01). In conclusion, H. Pylori cagA gene expression and the detection of 8-OHdG adducts in gastric epithelium can serve as potential early biomarkers of H. Pylori-associated gastric carcinogenesis.

Immunoglobulin M nephropathy in adults: a clinicopathological study.

INTRODUCTION: There is no data specifically on the clinical and immunopathologic features of Immunoglobulin M nephropathy (IgMN) in adults with kidney diseases in Pakistan. MATERIALS AND METHODS: We retrospectively reviewed our adult native renal biopsy records from May 2001 to April 2010 and identified 57 cases out of a total of 1,753 records labeled as IgMN on final histopathological analysis. Among these, 41 cases were included in the present analysis. Their relevant data items were collected from the case files and biopsy reports. RESULTS: The mean age of this cohort was 30.21 ± 10.12 years. The male-female ratio was 1.15:1. The most common presentation was idiopathic nephrotic syndrome. Hematuria and hypertension at presentation were noted in 24 (58.5%) and 10 (24.4%) patients, respectively. The most common morphologic change was glomerular mesangial cell proliferation, found in 28 biopsies (68.3%). Mesangial matrix expansion was noted in 16 (39%). Minor glomerular alterations were noted in 5 cases (12.2%) and focal segmental glomerulosclerosis in 4 (9.8%). Immunofluorescence microscopy showed diffuse mesangial positivity of IgM in all specimens. Subdominant IgA was noted in 6 cases (14.6%). Complements C3 and C1q were found in 28 (68.3%) and 21 (51.2%) patients, respectively. CONCLUSIONS: Our results show that IgMN is not very common in adults. Its clinicopathological spectrum is similar to that described from the neighboring countries, showing a spectrum of morphologic changes ranging from minor changes to focal segmental glomerulosclerosis.

Reticular type parotid myoepithelial carcinoma: an intriguing variant and mimicker.

Myoepithelial carcinoma, the malignant counterpart of benign myoepithelioma, is one of the rarest salivary gland neoplasms. It is composed almost exclusively of tumour cells with myoepithelial differentiation, characterized by infiltrative growth and potential for metastasis. We herein, report a case of myoepithelial carcinoma in a 50 years old male with reticular morphology. Reticular variant of myoepithelial carcinoma may be mistaken for a variety of benign and malignant epithelial and mesenchymal tumours including mixed tumour (pleomorphic adenoma), adenoid cystic carcinoma, basal cell adenoma and epithelial myoepithelial carcinoma. Complete surgical excision is the mainstay of therapy. The role of radiation therapy and chemotherapy is not yet established. Awareness of this variant is emphasized to prevent misdiagnosis.

Study of nephrotic syndrome in children: Importance of light, immunoflourescence and electron microscopic observations to a correct classification of glomerulopathies

Objective: To evaluate the contribution of electron microscopy (EM) to the accurate diagnosis of glomerulopathies in childhood nephrotic syndrome (NS) in a developing country. Methods: The study was carried out at the Histopathology Department, Sindh Institute of Urology and Transplantation (SIUT) from April 2007 to March 2008. All children (≤18 years) presenting with NS were included. Patients' demographic, clinical, laboratory, and biopsy data were retrieved from case records and biopsy reports. Renal biopsies were studied by light microscopy, immunoflourescence, and EM. Results: The mean age of 74 children was 11.34±4.85 years. EM was useful in 97.2% of cases, being essential in 31% and helpful in 66.2% cases. Conclusion: The results demonstrate that the ultrastructural study is both helpful and essential to a correct classification of glomerular diseases underlying NS in children in nearly all cases and whenever feasible this should be used in the pathologic evaluation of renal biopsies (AU)

Objetivo: Evaluar la contribución de la microscopía electrónica (ME) al diagnóstico preciso de las glomerulopatías en el síndrome nefrótico (SN) infantil en un país en vías de desarrollo. Método: El estudio se realizó en el Departamento de Histopatología del Instituto Sindh de Urología y de Trasplante (SIUT) desde abril de 2007 a marzo de 2008. En él se incluyeron todos los niños (≤ 18 años) que presentaban SN. Los datos demográficos, clínicos, de laboratorio y de la biopsia de los pacientes se obtuvieron a partir de expedientes de casos e informes de la biopsia. Las biopsias renales se estudiaron mediante microscopía de luz, inmunofluorescencia y ME. Resultados: La media de edad de 74 niños era de 11,34 ± 4,85 años. La ME resultó útil en el 97,2 % de los casos, siendo esencial en el 31 % y constituyendo una ayuda en el 66,2 % de los casos. Conclusión: Los resultados demuestran que el estudio ultraestructural es de utilidad y resulta esencial para la correcta clasificación de las enfermedades glomerulares subyacentes al SN infantil en casi todos los casos; por lo tanto, debería utilizarse en la evaluación patológica de biopsias renales siempre que fuera posible (AU)

Study of nephrotic syndrome in children: importance of light, immunoflourescence and electron microscopic observations to a correct classification of glomerulopathies.

OBJECTIVE: To evaluate the contribution of electron microscopy (EM) to the accurate diagnosis of glomerulopathies in childhood nephrotic syndrome (NS) in a developing country. METHODS: The study was carried out at the Histopathology Department, Sindh Institute of Urology and Transplantation (SIUT) from April 2007 to March 2008. All children (≤18 years) presenting with NS were included. Patients' demographic, clinical, laboratory, and biopsy data were retrieved from case records and biopsy reports. Renal biopsies were studied by light microscopy, immunoflourescence, and EM. RESULTS: The mean age of 74 children was 11.34, 4.85 years, EM was useful in 97.2% of cases, being essential in 31% and helpful in 66.2% cases. CONCLUSION: The results demonstrate that the ultrastructural study is both helpful and essential to a correct classification of glomerular diseases underlying NS in children in nearly all cases and whenever feasible this should be used in the pathologic evaluation of renal biopsies.

Frequency and clinicopathological characteristics of variants of primary focal segmental glomerulosclerosis in adults presenting with nephrotic syndrome.

BACKGROUND: There is no information on the frequency and clinicopathological presentation of the variants of primary focal segmental glomerulosclerosis (FSGS) in adults presenting with idiopathic nephrotic syndrome (INS) in Pakistan. OBJECTIVES: The aim of this study was to determine the frequencies of different histologic variants of primary FSGS with INS at our center and to compare our findings with those published in literature. PATIENTS AND METHODS: All consecutive adults (≥18 years) with INS, and diagnosis of FSGS on renal biopsies, were included. Their clinicopathological features at the time of presentation were retrieved and compared among the variants. RESULTS: There were 120 (65.2%) males and 64 (34.8%) females. The mean age was 30.62±12.02 years. The mean 24-hr urinary protein excretion was 4.69±2.36 grams. Microscopic hematuria was found in 30 (16.3%) patients. The mean serum creatinine was 1.58±0.87 mg/dL. At presentation, 128 (69.6%) patients were normotensive, while 56 (30.4%) exhibited hypertension. FSGS, not otherwise specified (NOS) was the predominant variant, comprising 76.6% of all; collapsing variant comprised 12%, tip variant, 9.8%, perihilar, 1.1%, and cellular, 0.5%. The mean number of glomeruli involved by segmental scarring was 3.41±2.87 and there was significant difference among the variants (p= 0.001). Arteriolopathy was found in 23.4 % cases and fibrointimal thickening of arteries in 18.5%. Tubular atrophy and interstitial fibrosis (IF/TA) was noted in 93% of cases. There was no significant difference in vasculopathy and IF/TA among the variants. CONCLUSIONS: Collapsing variant was the second most common variant following NOS and these findings are different from other regional studies.

The prevalence and clinicopathological profile of IgM nephropathy in children with steroid-resistant nephrotic syndrome at a single centre in Pakistan.

BACKGROUND: There is little information on the clinicopathological characteristics of IgM nephropathy (IgMN) in paediatric steroid-resistant nephrotic syndrome (SRNS) and its response to calcineurin inhibitors (CNI). MATERIAL AND METHODS: This study was conducted at Sindh Institute of Urology and Transplantation, from January 2009 to August 2011. All SRNS children who received renal biopsies were included. Relevant data were compared among minimal change disease (MCD) and IgMN. The response to CNI was analysed in detail in IgMN by groups (group 1: complete or partial remission; group 2: no response). RESULTS: The frequency of IgMN in 147 children with SRNS was 13.6%. Compared with MCD, there was a male preponderance in IgMN. Blood urea and serum creatinine both at presentation and at last follow-up were significantly higher in IgMN. Regarding subgroups of IgMN, systolic blood pressure (SBP), blood urea and serum creatinine were significantly higher in group 2 at presentation, while at last follow-up, SBP, diastolic blood pressure and proteinuria were higher in group 2. The prevalence and degree of mesangial proliferation, global glomerulosclerosis, interstitial fibrosis and tubular atrophy were significantly higher in group 2. CONCLUSIONS: IgMN is a common cause of paediatric SRNS and is significantly different from MCD. There is also a significant difference in clinical and laboratory parameters among responders and non-responders to CNI in IgMN.

The spectrum of histopathological lesions in children presenting with steroid-resistant nephrotic syndrome at a single center in Pakistan.

Steroid-resistant nephrotic syndrome (SRNS) is a common problem in pediatric nephrology practice. There is currently little information in the literature on the spectrum of histopathologic lesions in children presenting with SRNS in Pakistan. This study was designed to determine the histopathologic lesions in children presenting with SRNS at our center. The study was conducted at the Histopathology Department, Sindh Institute of Urology and Transplantation (SIUT) from January 2009 to August 2011. All children (≤ 16 years) presenting with SRNS, in whom renal biopsies were performed, were included. Their demographic, clinical, laboratory, and histopathological data were retrieved from files and original renal biopsy forms. The results were analyzed by SPSS version 10.0. A total of 147 children were included. Of these, 91 (61.9%) were males and 56 (38.1%) females, with male-to-female ratio of 1.6 : 1. The mean age was 7.03 ± 4.0 years (range: 6 months-16 years). The histopathological lesions seen on renal biopsies comprised of focal segmental glomerulosclerosis (FSGS) (38.5%), followed by minimal change disease (MCD) (23.2%), IgM nephropathy (IgMN) (13.6%), idiopathic mesangial proliferative GN (10.2%), membranous GN (8.2%), and mesangiocapillary GN (4.8%). Our results indicate that FSGS is the predominant lesion in children with SRNS, followed by MCD and IgMN.

A clinicopathologic study of primary focal segmental glomerulosclerosis in children.

There is very little information in the literature on the treatment and prognosis of primary focal segmental glomerulosclerosis (FSGS) among children in Pakistan. This is a review of 94 children (≤16 years) with a diagnosis of primary FSGS who presented to the Sindh Institute of Urology and Transplantation between 1995 and 2008. The clinical records and original renal biopsy reports were reviewed to determine demographic, clinical, laboratory and pathologic features. Renal biopsies were studied by light microscopy, immunofluoroscence and electron microscopy. Thera-peutic regimens and response to therapy were analyzed. Majority of the children (60, 63.8%) had steroid-dependant nephrotic syndrome (SDNS) and 33 (35%) had steroid-resistant nephrotic syndrome (SRNS). Cyclosphosphamide was used in SDNS, and this produced complete remission (CR) in 25/36 (69.4%), partial response (PR) in 4/36 (11%) and no response in 7/36 (19.4%) cases. Cyclosporine was used in SRNS and some SDNS children, and showed a CR in 30 (52.6%), PR in 20 (35%) and no response in seven (12.2%) cases. Tacrolimus was used in seven (7.44%) children. CR was obtained in two (28.5%) and PR in five (71.4%) cases. Renal insufficiency developed in 12 (12.7%) children. Results from this study show that majority of the children with primary FSGS at our center could achieve high rates of sustained remission with second- and third-line immunosuppressive therapies with fairly good prognosis.

A spectrum of novel NPHS1 and NPHS2 gene mutations in pediatric nephrotic syndrome patients from Pakistan.

BACKGROUND: Mutations in the NPHS1 and NPHS2 genes are among the main causes of early-onset and familial steroid resistant nephrotic syndrome respectively. This study was carried out to assess the frequencies of mutations in these two genes in a cohort of Pakistani pediatric NS patients. METHODS: Mutation analysis was carried out by direct sequencing of the NPHS1 and NPHS2 genes in 145 nephrotic syndrome (NS) patients. This cohort included 36 samples of congenital or infantile onset NS cases and 39 samples of familial cases obtained from 30 families. RESULTS: A total of 7 homozygous (6 novel) mutations were found in the NPHS1 gene and 4 homozygous mutations in the NPHS2 gene. All mutations in the NPHS1 gene were found in the early onset cases. Of these, one patient has a family history of NS. Homozygous p.R229Q mutation in the NPHS2 gene was found in two children with childhood-onset NS. CONCLUSIONS: Our results show a low prevalence of disease causing mutations in the NPHS1 (22% early onset, 5.5% overall) and NPHS2 (3.3% early onset and 3.4% overall) genes in the Pakistani NS children as compared to the European populations. In contrast to the high frequency of the NPHS2 gene mutations reported for familial SRNS in Europe, no mutation was found in the familial Pakistani cases. To our knowledge, this is the first comprehensive screening of the NPHS1 and NPHS2 gene mutations in sporadic and familial NS cases from South Asia.

Pathology of idiopathic nephrotic syndrome in children: are the adolescents different from young children?

BACKGROUND: There is no specific data on the pathological lesions underlying idiopathic nephrotic syndrome (INS) in adolescents in Pakistan. Moreover, it is not known whether the pathological lesions in adolescents differ significantly from young children with INS in our setup. Materials and methods. A retrospective analysis was carried out on all patients with INS with onset ≤ 18 years of age. They were split into two groups: patients with onset of INS ≤ 12 years (young children group) and patients with onset ≥ 13 through 18 years of age (adolescent group). Renal biopsies were evaluated by light microscopy, immunoflourescence and electron microscopy. The histopathological lesions on renal biopsies were analyzed and compared between the two groups. RESULTS: The adolescents comprised 173 (32.1%) patients, and there were 365 young children (67.8%). The mean age of adolescents at the time of onset of INS was 15.12 ± 1.5 years and there were 113 boys (65.3%) and 60 girls (34.6%). The mean age of young children was 7.26 ± 3.24 years and there were 231 boys (63.2%) and 134 girls (36.7%). Focal segmental glomerulosclerosis was the most common histopathological lesion in adolescents (36.4%) followed by minimal change disease (MCD) (28.9%). Adolescent-onset INS had a significantly higher frequency of membranous glomerulonephritis and membranoproliferative glomerulonephritis (MPGN) (P < 0.05) and significantly lower frequency of MCD (P < 0.05) than early childhood-onset INS. CONCLUSIONS: Our data indicate that the pathological lesions in adolescent INS are different from younger children and resemble more closely those seen in adults. Our findings are concordant with the few previously published studies on this subject.

Raised serum creatinine at presentation does not adversely affect steroid response in primary focal segmental glomerulosclerosis in adults.

BACKGROUND: There is no information in international literature on the mode of presentation, laboratory and clinical features, treatment and prognosis of primary focal segmental glomerulosclerosis (FSGS) in adults in Pakistan. METHODS: This is a retrospective review of 124 adults (≥17 years) with a diagnosis of primary FSGS who presented to the adult nephrology clinic at Sindh Institute of Urology and Transplantation between January 1995 and June 2006. The clinical records and biopsy reports were reviewed to determine the demographic, clinical, laboratory and pathologic features, treatment responses and outcome of the disease. Renal biopsies were performed and evaluated by light microscopy, immunofluorescence and electron microscopy. Standard therapeutic regimens and response to therapy definitions were used. Outcome data were obtained at last follow-up. RESULTS: Mean age of all patients was 30.9 ± 13.6 years (range: 17-85 years). Of these, 86 (69%) were males and 38 (31%) females, with a male to female ratio of 2.2:1. Of 124 patients, 79 (63.7%) were treated with steroids for a median duration of 5 months. Remission was achieved in 40 (50.6%) patients. Relapse occurred in 14 (17.7%) steroid-treated patients. These achieved sustained remission with retreatment. None of the steroid-treated patients went into end-stage renal disease over a mean follow-up of 2.3 years. CONCLUSIONS: Results from this study show that half of adults with primary FSGS achieve sustained remission with prolonged steroid treatment and consequently exhibit an excellent prognosis for long-term outcome. Moreover, raised serum creatinine at presentation does not in itself adversely affect steroid response in adults with primary FSGS.