Modulation of Renal Parenchyma in Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells Transplantation in Acute Kidney Injury

BACKGROUND AND OBJECTIVES: In regenerative medicine, mesenchymal stem cells derived from adipose tissues (Ad-MSCs) are a very attractive target to treat many diseases. In relation to nephrology, the aim of the current study is to investigate the effects of Ad-MSCs for the amelioration of acute kidney injury and to explore the mechanism of renal parenchymal changes in response to allogeneic transplantation of Ad-MSCs. METHODS AND RESULTS: The nephrotoxicity was induced by cisplatin (CP) in balb/c mice according to RIFLE Class and AKIN Stage 3. PCR, qRT-PCR and fluorescent labeled cells infusion, histopathology, immunohistochemistry, functional analyses were used for genes and proteins expressions data acquisition respectively. We demonstrated that single intravenous infusion of 2.5×107/kg mAd-MSCs in mice pre-injected with CP recruited to the kidney, restored the renal structure, and function, which resulted in progressive survival of mice. The renal tissue morphology was recovered in terms of diminished necrosis or epithelial cells damage, protein casts formation, infiltration of inflammatory cells, tubular dilatation, and restoration of brush border protein; Megalin and decreased Kim-1 expressions in mAd-MSCs transplanted mice. Significant reduction in serum creatinine with slashed urea and urinary protein levels were observed. Anti-BrdU staining displayed enhanced tubular cells proliferation. Predominantly, downgrade expressions of TNF-α and TGF-β1 were observed post seven days in mAd-MSCs transplanted mice. CONCLUSIONS: Ad-MSCs exerts pro-proliferative, anti-inflammatory, and anti-fibrotic effects. Ad-MSCs transplantation without any chemical or genetic manipulation can provide the evidence of therapeutic strategy for the origin of regeneration and overall an improved survival of the system in functionally deprived failed kidneys.

Transperineal template-guided prostate saturation biopsies in men with suspicion of prostate cancer: a pilot study from Pakistan

Traditionally, transrectal ultrasound (TRUS)-guided biopsies are done for the diagnosis of prostatecancer (PCa) in Pakistan. The transperineal template-guided saturation biopsy (TTSB) approach hasbeen recently introduced in Pakistan and we share diagnostic yields and pathological findings ofspecimens taken for PCa diagnosis in men with elevated serum total prostate specific antigen (PSA)and negative TRUS-guided prostate biopsies. In all, 16 patients investigated at the Department ofUrology, Sindh Institute of Urology and Transplantation (SIUT), underwent TTSB. The mean ageof patients was 67.8 ± 8.8 (range: 55 - 84) years. The median PSA was 9.5 (IQR: 7.9 - 19.8) ng/ml. The duration of symptoms before biopsy ranged from 1 month to 144 months. The prostatewas enlarged with mean weight of 73.5 ± 55.5 g. Histopathology revealed PCa in 5 of 16 (31.2%)cases. The Gleason score was 6 (3+3), 7 (3+4) and 8 (4+4) in 1 case each (6.3%) and 10 (5+5) in 2cases (12.5%). At least two cores were positive in all positive cases. None of the patients requiredantibiotics post-procedure. In conclusion, the TTSB technique is a promising option for patients withelevated PSA level and negative transrectal prostate biopsies for the detection of PCa in our settin

Clinicopathological study of seronegative celiac disease in adults in Pakistan: a pilot study

Background: celiac disease [CD] is usually missed, if the serology is negative. We aimed to evaluate the clinicopathological characteristics of seronegative CD [SNCD] and its response to gluten-free diet [GFD] in adult patients

Methods: this observational study was carried out at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan from 2009 to 2015. All consecutive adult patients [>/=17 years] with features of marked villous atrophy [Marsh class>/=III] on duodenal biopsy, negative tissue transglutaminase IgA and IgG antibodies [anti-tTg IgA and IgG] and human leukocyte antigen [HLA] DQ2 or DQ8 serotypes were studied. Clinical characteristics, laboratory parameters, and response to GFD were analyzed by SPSS software version 20. Median and interquartile range [IQR] were used for summarizing quantitative data. Frequency [percentages] was used for qualitative data

Results: a total of 12 patients with median age of 31.5 years [IQR: 19.75-46.75 years], of whom five [41.6%] were men were studied. The presenting complaints were: weight loss in 11 [91.6%] and abdominal pain in 9 [75%] patients. Anemia was observed in 10 [83.3%] patients with median hemoglobin of 9.5 g/dL [IQR: 6.3-13.25 g/dL]. Median alanine transaminase [ALT] was 21 U/L [IQR: 13-27 U/L] and median albumin was 3 g/dL [IQR: 2.4-3.6 g/dL]. Anti-tTg IgA and IgG were negative in all patients. HLA DQ serotyping showed homozygous DQ2 and DQ8 in four and one patients, respectively; while heterozygous DQ2 and DQ8 in five and two patients, respectively. All patients were advised to receive GFD. Nine [75%] patients showed complete clinical response. Two patients were non-compliant and one with non-alcoholic fatty liver disease [NAFLD]-related cirrhosis had partial clinical response. Out of the nine responders, two patients showed response within 6 months while the remaining showed improvement over a year period

Conclusion: the diagnosis of SNCD is rewarding as it responds favorably to GFD in most patients. HLA serology provides an important tool for diagnosis of this entity

Coexistence of celiac and crohn's disease in a patient presenting with chronic diarrhea

Celiac disease [CD] is one of the most common causes of malabsorption. It is an immune-mediated disease manifested by diarrhea, steatorrhea, flatulence, and weight loss, caused by ingestion of gluten containing diets. The disease has typical small intestinal biopsy features of villous atrophy, crypt hyperplasia, and intense inflammation of the mucosal layer. The disease is rarely associated with Crohn's disease [CRD]. Studies on the impact of CD on the natural history of inflammatory bowel disease [IBD] have shown that the natural course of CRD is not influenced by coexistent CD. We report a case of 54-year female who presented with diarrhea and weight loss. On initial evaluation, CD was diagnosed, and responded to gluten-free diet [GFD]. Later on, she developed joint pains and her diarrhea recurred. Further evaluation revealed coexistence of CRD. The treatment of CRD was also initiated and this led to marked improvement in the symptoms of the patient

Proliferative lesions of parathyroid glands: an update for practicing pathologists

Pathological lesions of parathyroid glands encompass a wide range of lesions ranging from developmental anomalies to inflammatory disorders to neoplastic processes. Proliferative lesions of parathyroid glands represent the commonest causes of hyperparathyroidism in clinical practice. However, the parathyroid specimens represent only a tiny fraction of the workload received in a non-specialist histopathology laboratory. As a result, the familiarity of the pathologists with the spectrum of parathyroid lesions is generally limited. An accurate diagnosis of the parathyroid lesions is challenging and a daunting task for both the clinicians and the pathologists. The traditional morphological approaches have limitations. Ancillary techniques of immunohistochemistry and molecular biology are being increasingly employed to resolve the diagnostic dilemmas. This review briefly describes the proliferative pathological lesions affecting the parathyroid glands and provides some useful tips on accurately diagnosing these lesions

Gitelman's syndrome complicated by mild renal insufficiency and high anion gap acidosis; a rare presentation in a young female

Gitelman's syndrome [GS] is a rare autosomal recessive renal tubular disorder that is characterized by episodic clinical manifestations and persistent biochemical abnormalities. The disorder manifests in adolescent or adult age and is characterized by transient episodes of muscle weakness and tetany. Its diagnosis requires a high index of suspicion and skillful interpretation of laboratory investigations. We herein present a case of a 20-year-old female patient who presented with generalized muscle weakness and mild renal insufficiency. Laboratory investigations revealed mild azotemia, high anion gap acidosis, hypokalemia, hypomagnesemia, and hypocalciuria. She recovered her renal functions and muscle power with appropriate management and is doing well seven months after her first presentation to our hospital. This case highlights the need to create high index of suspicion among the general practitioners about this syndrome and an early referral of such patients to nephrologists for an accurate diagnosis and appropriate management

Journal of Nephropathology: a need of the hour

Nephropathology is a rapidly evolving field which is at the forefront of modern research because of the growing epidemic of kidney disease throughout the world. Kidneys also constitute the most common solid organs for transplantation in patients suffering from end-stage renal disease [ESRD]. As a result, renal transplant pathology has similarly emerged as one of the leading domains of the subspecialty of nephropathology

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

IgA nephropathy [IgAN] is the most common glomerulopathy worldwide. The most significant development in IgAN research in the recent past consists of promulgation of the Oxford-MEST classification. The classification represents an entirely unique approach in the classification of renal diseases. 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

IgA nephropathy: an update on pathogenesis and classification

IgA nephropathy is a primary glomerulopathy characterized by deposition of IgA containing immune deposits in the kidney. Its diagnosis is based on histopathologic and immunoflourescence studies on renal biopsy. The disorder is poorly understood. This review is focused on updates regarding its pathogenesis and discussion on a new proposed histopathological classification of IgA nephropathy

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

Peripheral primitive neuroectodermal tumor/Ewing's 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