Muhammed Mubarak

A Renal Transplantation Model for Developing Countries

The estimated incidence of end‐stage renal disease (ESRD) in Pakistan is 100 per million population. Paucity and high costs of renal replacement therapy allows only 10% to get dialysis and 4–5% transplants. Our center, a government organization, started a dialysis and transplant program in 1980s where all services were provided free of charge to all patients. It was based on the concept of community government partnership funded by both partners. The guiding principles were equity, transparency, accountability and development of all facilities under one roof. This partnership has sustained itself for 30 years with an annual budget of

Oxford classification of IgA nephropathy: Broadening the scope of the classification.

25 million in 2009. Daily 600 patients are dialyzed and weekly 10–12 receive transplants. One‐ and 5‐year graft survival of 3000 transplants is 92% and 85%, respectively. The institute became a focus of transplantation in Pakistan and played a vital role in the campaign against transplant tourism and in promulgation of transplant law of 2007, and also helped to increase altruistic transplants in the country. This model emphasizes that in developing countries specialized centers in government sector are necessary for transplantation to progress and community support can make it available to the common man.

Clinicopathologic characteristics and steroid response of IgM nephropathy in children presenting with idiopathic nephrotic syndrome.

IgA nephropathy (IgAN) is the most common glomerulopathy worldwide (1). However, its prevalence in published renal biopsy series and clinicopathological features vary from region to region, and country to country (2). This is mainly due to differences in biopsy indications, the extent of pathological evaluation of renal biopsies and the nephrology practice, rather than true ancestral differences in the prevalence of the disorder (3). The disease is most prevalent in countries with population-based urinalysis screening programs. Similarly, the clinicopathological presentation of the disease is milder in centers employing the urinalysis approach for the diagnosis of the disorder (2,3). Although, in the majority of patients, the disease is benign, IgAN is characterized by a slowly progressive course to end-stage renal disease (ESRD) in 30-40% of individuals over 20-years of follow-up (2). This progression is unpredictable in most instances. There are no entirely reliable factors which can accurately predict the progression in individual patients (4). Traditionally, the prognostication was carried out using the clinical and laboratory parameters. Pathological features on renal biopsy have remained largely controversial till recent past (5,6). Consequently, one of the active areas of research in IgAN at present involves the determination of precise factors which can accurately and reliably predict the prognosis and response to treatment in individual patients (7). There is relatively little information in literature on the population-based prevalence and clinicopathological features of IgAN in third world countries (3,8-10). In particular, there are very few studies on the pathological characteristics of the disease according to the new Oxford-MEST classification from these parts of the world (8). The most significant development in IgAN research in the recent past consists of promulgation of the Oxford-MEST classification (5,6,11,12). The classification represents an entirely unique approach in the classification of renal diseases. Although, the classification is robust, evidence-based, prevalidated, and international in outlook, there were some limitations in the original cohort used for the study (11,12). It was retrospective collected, included select cases, excluded milder and rapidly progressive cases, and there was no representation of south Asian or Middle Eastern countries. The authors of the original classification and other researchers suggested validating the classification in different settings and in prospective cohorts of patients with the disease in routine clinical practice (5,6,11,12). In this context, a number of validation studies have been published and attest to the usefulness of this classification in the routine clinical practice and the better reproducibility of the classification (13-18). Slight deviations and differences have also been reported, reflecting the diversity of the cases of IgAN in different centers, but overall results are concurrent with the original Oxford study (13-18). Nasri et al. have done a commendable job by exploring the new aspects of IgAN pathology in Iranian patients (19). The authors have analyzed the clinicopathological features in relation to the Oxford classification of IgAN in 102 patients over three years of study. There are many strong points in the study. The number of patients analyzed is fairly large. The study population is racially homogeneous, consisting of Iranian patients except for two Afghans. No pre-biopsy treatment was given in any case, thus eliminating the confounding variable of treatment effect on the disease morphology and classification. The authors found a higher prevalence of segmental glomerulosclerosis and mild to moderate interstitial fibrosis/tubular atrophy (IFTA) in the study cohort. These same features were significantly more prevalent in males as compared with females, attesting to the poor outcome of the disease in male patients. Segmental glomerulosclerosis is frequently seen in IgAN in many parts of the world and is indeed the common pattern in third world countries. It is also an adverse prognostic indicator in the Oxford classification (3). The authors also found a fair correlation of crescents with serum creatinine (Spearman’s rho=0.386) and propose that this lesion should be included in the future versions of the Oxford classification (19). Indeed, the predictive value of this lesion could not be assessed in the original study cohort of patients used for the development of the original classification, because of its rarity (5). A number of other investigators have also addressed the issue of extracapillary epithelial proliferation in IgAN and suggested that, this lesion should be included in the next version of the Oxford classification of IgAN to widen the scope of the classification (13). There are a number of limitations and caveats in the study too. The study is, in effect, a cross-sectional analysis of IgAN cases, and there is no information on the follow-up or outcome of the patients under study. One of the important objectives of the Oxford classification is the prognostication of the disease course in patients with IgAN, which has not been undertaken in this study. We hope that the authors will continue their work on long-term follow-up of this cohort with properly defined outcomes for future analysis. There are also no data on the treatment of these patients. The authors also did not correlate the morphological features with immunoflourescence (IF) features. This aspect has been addressed recently by Bellur et al. in the original study cohort used for developing the Oxford classification (20). The ongoing and future research should address the issues of combining the clinical, laboratory, histopathological, molecular biological and genetic data, to devise algorithms for individualized decisions of treatment choice for patients with IgAN, and accurate prognostication (11). In summary, Nasri et al. deserve congratulations for shedding light on newer pathological aspects of IgAN in Iranian patients according to the Oxford classification. Such studies will go a long way in further refining the original Oxford classification and broadening its scope and ultimately helping the individualized patient management and prognostication throughout the world.

The Spectrum of Histopathological Lesions in Children Presenting with Steroid-Resistant Nephrotic Syndrome at a Single Center in Pakistan

Mubarak M, Kazi JI, Shakeel S, Lanewala A, Hashmi S, Akhter F. Clinicopathologic characteristics and steroid response of IgM nephropathy in children presenting with idiopathic nephrotic syndrome, APMIS 2011; 119: 180–186.

Primitive neuroectodermal tumor/Ewing's sarcoma in adult uro-oncology: A case series from a developing country

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.

Pattern of renal diseases observed in native renal biopsies in adults in a single centre in Pakistan

Peripheral primitive neuroectodermal tumor/Ewings sarcoma (PNET/EWS) is primarily a tumor of soft tissues and bones. Primary localization of PNET/EWS in genitourinary organs is rare. No data on this localization of PNET/EWS are available in literature from Pakistan. We searched our adult uro-oncology records from 1994 till date and identified all cases of adult genitourinary and adrenal PNET/EWS diagnosed on histology and immunohistochemistry. Their case records were reviewed to obtain data on demographics, presentation, pathologic features, management and outcome. Six cases were found; all were young and had aggressive disease at presentation. Four had renal PNET/EWS. One case each of prostate and adrenal PNET/EWS was seen. Surgery and chemotherapy formed the mainstay of management. Three patients (50%) died during treatment, two were lost to follow-up and one case with renal PNET/EWS showed good initial response to chemotherapy but was later on lost to follow-up. In conclusion, PNET/EWS should be considered in the differential diagnosis of genitourinary malignant tumors in young patients. These tumors are aggressive with poor outcome.

Histological patterns of idiopathic steroid resistant nephrotic syndrome in Egyptian children: A single centre study.

Aim:  In the absence of a national renal biopsy registry, there is a paucity of information on the pattern of renal disease observed in native renal biopsies in adults in Pakistan.

What nephrolopathologists need to know about antiphospholipid syndrome-associated nephropathy: Is it time for formulating a classification for renal morphologic lesions?

BACKGROUND BACKGROUND Idiopathic steroid resistant nephrotic syndrome (ISRNS) represents about 10-20% of children with nephrotic syndrome with variable outcome. OBJECTIVES To determine the histological patterns of ISRNS in Egyptian children and the histological details of the commonest types which might be the reason for the steroid resistance. PATIENTS AND METHODS The study included 53 cases with ISRNS. Their renal biopsies were retrieved from the archive of Electron microscopy unit and pathology department, Ain Shams University Specialized Hospital (ASUSH) in the duration from 2005-2011. The biopsies were examined histologically, with immunohistochemistry, and by electron microscopy. RESULTS They were 36 males (67.9%) and 17 females (32.1%), the age at diagnosis ranged from 1.5- 16 years with a mean of 6.71 years. Lower limb oedema was the commonest presentation (100%), haematuria was revealed in (17%) of cases. Histological examination showed three major patterns; Focal segmental glomerulosclerosis (FSGS) in 30.2%, minimal change glomerulopathy (MCG) in 24.5% and IgA nephropathy in 13.2 %. Mesangial hypercellularity was very common among MCG patients (85.3% ±6.7). Tubulointerstitial inflammation and fibrosis were common among cases with IgA nephropathy (40.4% ±11, 53.7% ±8 respectively). CONCLUSIONS ISRNS in Egyptian children could be attributed mainly to three major diseases (FSGS, MCG and IgA nephropathy). Mesangial hypercellularity and severe tubulointerstitial disease might be the major causes for steroid resistance in MCG and IgA nephropathy respectively. Renal biopsy with electron microscopy examination should be done for all children with nephrotic syndrome at first time of presentation for proper assignment of treatment protocol.

Pediatric Kidney Transplantation in the Developing World: Challenges and Solutions

CONTEXT Antiphospholipid syndrome (APS) is a systemic autoimmune disorder which commonly affects kidneys. EVIDENCE ACQUISITIONS Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. RESULTS There is sufficient epidemiological, clinical and histopathological evidence to show that antiphospholipid syndrome is a distinctive lesion caused by antiphospholipid antibodies in patients with different forms of antiphospholipid syndrome. It is now time to devise a classification for an accurate diagnosis and prognostication of the disease. CONCLUSIONS Now that the morphological lesions of APSN are sufficiently well characterized, it is prime time to devise a classification which is of diagnostic and prognostic utility in this disease.

Significance of immunohistochemical findings in Oxford classification of IgA nephropathy: The need for more validation studies

The prevalence of pediatric RRT and transplantation are low in developing countries, 6–12 and <1 to 5 per million child population (pmcp), respectively. This is due to low GDP/capita of <