Journal of nephropathology
Volume:2 Issue: 3, Jul 2013

Context: There is a need to define the exact benefits and contraindications of use of high-dose recombinant human erythropoietin (EPO) for its non-hematopoietic function as a cytokine that enhances tissue repair after injury. This review compares the outcomes from use of EPO in the injured heart and kidney, two organs that are thought, traditionally, to have intrinsically-different repair mechanisms.Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Ongoing work by us on EPO protection of ischemia-reperfusion-injured kidneys indicated, first, that EPO acutely enhanced kidney repair via anti-apoptotic, pro-regenerative mechanisms, and second, that EPO may promote chronic fibrosis in the long term. Work by others on the ischaemia-injured heart has also indicated that EPO promotes repair. Although myocardial infarcts are made up mostly of necrotic tissue, many publications state EPO is anti-apoptotic in the heart, as well as promoting healing via cell differentiation and stimulation of granulation tissue. In the case of the heart, promotion of fibrosis may be advantageous where an infarct has destroyed a zone of cardiomyocytes, but if EPO stimulates progressive fibrosis in the heart, this may promote cardiac failure. A major concern in relation to the use of EPO in a cytoprotective role is its stimulation of long-term inflammation and fibrosis. EPO usage for cytoprotection is undoubtedly advantageous, but it may need to be offset with an anti-inflammatory agent in some organs, like kidney and heart, where progression to chronic fibrosis after acute injury is often recorded.

Apoptosis, reactive oxygen species (ROS) and inflammatory cytokines have all been implicated in the development of Alzheimer’s disease (AD). The present study identifies the apoptotic factor that was responsible for the fourfold increase in apoptotic rates that we previously noted when pig proximal tubule, LLC-PK1, cells were exposed to AD plasma as compared to plasma from normal controls and multi-infarct dementia.Patients and The apoptotic factor was isolated from AD urine and identified as lipocalin-type prostaglandin D2 synthase (L-PGDS). L-PGDS was found to be the major apoptotic factor in AD plasma as determined by inhibition of apoptosis approximating control levels by the cyclo-oxygenase (COX) 2 inhibitor,NS398, and the antibody to L-PGDS. Blood levels of L-PGDS, however, were not elevated in AD. We now demonstrate a receptor-mediated uptake of L-PGDS in PC12 neuronal cells that was time, dose and temperature-dependent and was saturable by competition with cold L-PGDS and albumin. Further proof of this endocytosis was provided by an electron microscopoic study of gold labeled LPGDS and immunofluorescence with Alexa-labeled L-PGDS. The recombinant L-PGDS and wild type (WT) L-PGDS increased ROS but only the WTL-PGDS increased IL6 and TNFα, suggesting that differences in glycosylation of L-PGDS in AD was responsible for this discrepancy. These data collectively suggest that L-PGDS might play an important role in the development of dementia in patients on dialysis and of AD.

Antiphospholipid antibodies (aPL) are autoantibodies that are associated with a clinical state of hypercoagulability and diverse clinical manifestations collectively known as antiphospholipid syndrome (APS). To investigate the prevalence of anti-beta2glycoproteinI-antibodies (anti-β2GPI) and their isotypes in patients with renal diseases and clinical suspicion of antiphospholipid syndrome (APS).Patients and This is a retrospective study in which we have analyzed the prevalence of anti-β2GPI and its isotypes in 170 patients on initial testing and in 29 patients repeated after 12 weeks for confirmation of APS. The clinical information was provided by the treating physicians or retrieved from the clinical records. The tests for anti-β2GPI screening and its isotypes (IgG, IgM and IgA) detection were assessed. On initial samples, anti-β2GPI was positive in 118patients. IgA-β2GPI positivity (93; 79%) was significantly higher than IgM and IgG isotypes. Out of anti-β2GPI positive patients, clinical features in 95 patients were suggestive of APS or had SLE. Of these, IgA isotypes was found in 66% (P = 0.010), IgM in 31% (P = 0.033), and IgG in 11% (P = 0.033). On repeat testing, anti-β2GPI was persistently found In 22 patients with a continual predominance of IgA-anti- β2GPI over IgM and IgG isotypes (91% vs. 45.5% and 18% respectively). Our results show that IgA-anti-β2GPI antibodies are the most prevalent isotypes in patients with renal disease or on renal replacement therapy in our population. Thus inclusion of IgA-anti-β2GPI in the testing repertoire may increase the diagnostic sensitivity for APS in patients with renal diseases.

Oxford classification for IgA nephropathy (IgAN) did not include pattern of immunostaining in the analysis. The aim of this study is to determine the potential correlation between the immunostaining data and morphologic variables of Oxford classification (MEST) and various clinical and demographic data of patients with IgAN.Patients and The pathologic diagnosis of IgAN requires the demonstration of IgA-dominant mesangial or mesangio-capillary immune deposits through immunofluorescence (IF) microscopy. The immune deposits were semiquantitatively assessed as 0 to 3+ positive bright. These were correlated with various clinical, demographic and histological variables of Oxford classification. A total of 114 biopsies were enrolled to the study (70.2% were male). Mean age of the patients was 37.7 ± 13.6 years. This study showed that, only C3 deposits had a significant correlation with serum creatinine. Other antibodies (IgA, IgM and IgG) had no significant association with serum creatinine. This study also showed that IgA deposition score had significant positive association with endocapillary proliferation (E) and segmental glomerulosclerosis (S) variables of Oxford classification. Moreover, IgM deposition score had positive association with S variable. There was no significant association of IgG deposition score with four morphologic variables of Oxford classification. There was significant association of C3 deposition score with S and E variables too. The significant relationships of IgA and C3 deposits with some of the Oxford variables need more attention. We propose to further investigate this aspect of IgAN disease.

Systemic AA amyloidosis is a long-term complication of several chronic inflammatory disorders. Organ damage results from the extracellular deposition of proteolytic fragments of the acute-phase reactant serum amyloid A (SAA) as amyloid fibrils. Drug users that inject drug by a subcutaneous route (“skin popping”) have a higher chance of developing secondary amyloidosis. The kidneys, liver, and spleen are the main target organs of AA amyloid deposits. More than 90% of patients with renal amyloidosis will present with proteinuria, nephrotic syndrome, or renal dysfunction. A 37 year-old female presented to the hospital with a one-weekhistory of pain and redness in her right axilla. Her relevant medical history included multiple skin abscesses secondary to “skin popping”, heroin abuse for 18 years, and hepatitis C. The physical examination revealed “skin popping” lesions, bilateral costovertebral angle tenderness, and bilateral knee swelling. The laboratory workup was significant for renal insufficiency with a serum creatinine of 5 mg/dL and 14.8 grams of urine protein per 1 gram of urine creatinine. The renal biopsy findings were consistent with a diagnosis of renal amyloidosis due to serum amyloid A deposition and acute tubulointerstitial nephritis. AA renal amyloidosis among heroin addicts seems to be associated with chronic suppurative skin infection secondary to “skin popping”. It is postulated that the chronic immunologic stimulation by one or more exogenous antigens or multiple acute inflammatory episodes is an important factor in the pathogenesis of amyloidosis in these patients. Therefore, AA renal amyloidosis should always be considered in chronic heroin users presenting with proteinuria and renal impairment.

C1q nephropathy (C1qN) is an uncommon glomerulopathy with asignificant deposition of C1q in mesangium without clinical evidence of lupus.bAccording to the best of our knowledge, there is not any report on coincidencebof diabetes mellitus and C1qN. In this report, we presented a 28 years-old-patient with type 1bdiabetes and nephrotic range proteinuria, glomerular hematuria and C1q glomerulopathybin renal biopsy. According to the best of our knowledge, there is no previous reportbabout the association between type 1 DM and C1qN. Prevalence of autoimmunebdisease is higher in type 1 DM and this may explain the relation between DM andbC1qN in our patient.

Acute tubular necrosis and pigment induced kidney injury are well described consequences of cocaine abuse. However, acute interstitial nephritis associated with cocaine use has been previously reported in only three patients. We present the case of a 49-year-old man who developed acute kidney injury from biopsy-proven interstitial nephritis after nasal insufflation of cocaine. Unlike prior reports, our patient remained non-oliguric and did not require renal replacement therapy. Interstitial nephritis should be considered as a potential cause of acute kidney injury associated with cocaine use. The approach to management of cocaine associated acute kidney injury (AKI) may be different in patients with interstitial nephritis than for those with tubular necrosis or pigment induced renal injury.

Implication for health policy/practice/research/medical education:Oxford classification of IgA nephropathy (IgAN) has been validated as clinically useful tool for prognostication of individual patients with IgAN. The original classification did not address the significance of immunostaining pattern in IgAN. A subsequent study by the same authors found immunostaining data to be potentially useful in predicting some of the morphological variables of Oxford classification. The study under discussion also addresses the potential significance of these ancillary data in refining the individual prognostication in this disease.Please cite this paper as: Mubarak M. Significance of immunohistochemical findings in Oxford classification of IgA nephropathy: The need for more validation studies. J Nephropathology. 2013; 2(3): 210-213. DOI: 10.5812/nephropathol.11089