Journal of nephropathology
Volume:6 Issue: 2, Apr 2017

Pemetrexed (PEM) is a new-generation multitargeted antifolate agent with a demonstrated broad-spectrum activity in several types of human cancers, including non-small cell lung cancer (NSCLC) and mesothelioma. Major side effects include dose-limiting hematologic toxicities. PEM nephrotoxicity is well known; however, its frequency is considered to be low.
Here we report two cases of acute kidney injury (AKI) related to PEM administration (500 mg/m2) in patients with NSCLC. The first patient required hemodialysis treatment and was submitted to renal biopsy which showed acute tubular damage and interstitial edema without acute tubular necrosis. No other potential nephrotoxic agents were identified. The second patient developed AKI, not proven by biopsy and did not require renal replacement therapy. Both patients, on regular supplementation with folic acid and vitamin B12, concomitantly developed myelosuppression and even several months after PEM withdrawal, showed only a modest improvement of renal function.
PEM is an antifolate antineoplastic agent with a broad-spectrum activity in locally advanced or metastatic NSCLC. It has been shown that PEM allows longer survival. The risk of acute or chronic kidney disease may be one of the prices to be paid for this success.

Primary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare malignancy. We found only 8 cases of MALT lymphoma in literature.
We report here another case of primary prostatic MALT lymphoma which is presented by hematuria and diagnosed primarily as BPH. Immunohistochemistry studies demonstrate the diagnosis and MALT lymphoma. Six months after starting the treatment the patient was alive and well.
Prostatic MALTomas are mainly presented with urinary obstruction or hematuria and have an indolent growth with a good prognosis.

Acute interstitial nephritis (AIN) is a clinico-pathological syndrome associated with a variety of infections, drugs, and sometimes with unknown causes. It is a common cause of acute kidney injury (AKI) and subsequent renal impairment, which often times is under-diagnosed. Infection-associated AIN occurs as a consequence of many systemic bacterial, viral, and parasitic infec-tions; however, its incidence has decreased significantly after the advent of antimicrobials. Infection-associated AIN presents with both oliguric or non-oliguric renal insufficiency, without the classical clinical triad of AIN (fever, rash, and arthralgia). In this scenario the renal function is usually reversible after the infection is treated. In most cases, patients with acute renal failure present with extra-renal manifestations typically detected in underlying infections. Renal biopsy serves as the most definitive test for both the diagnosis and prognosis of AIN.
In this paper, we will address one such case of biopsy-proven AIN. In this case, the patient presented with severe AKI induced by anaerobic streptococcus, leading to a periodontal abscess, which was successfully treated with corticosteroids and requiring renal replacement therapy (RRT).
AIN should be considered in the differential for unexplained AKI. Initial management should include conservative therapy by withdrawing any suspected causative agent. Renal biopsy is needed for confirmation in cases where kidney function fails to improve within 5–7 days on conservative therapy. Risk of immunosuppression is very important to consider when giving steroids in patients with infection induced AIN, and steroids may have to be delayed until the active infection is completely controlled.

Renal involvement in rheumatoid arthritis (RA) is common and has a negative impact on patient survival. Only few cases have been reported of necrotizing glomerulonephritis (GN) associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) in patients with RA.
We report a patient with RA who developed a necrotizing GN associated with ANCA-MPO, treated with rituximab (RTX). A 55-year-old man with a 27-year history of RA under secukinumab was referred to our nephrology clinic with worsening renal function associated with microhematuria and proteinuria. Our laboratory evaluation showed hypocomplementemia and positive titers for MPO-ANCA (615 U/mL). A renal biopsy demonstrated pauci-immune necrotizing GN. The patient was treated with 3 consecutive pulses of methylprednisolone followed by oral prednisolone (1 mg/Kg) and rituximab (1000 mg, repeated 14 days later). After a 10-month follow-up, the arthritis remains well-controlled, renal function stabilized, proteinuria improved and MPO-ANCA titer normalized (6.3 U/mL).
Necrotizing GN is a rare but a serious condition and an early diagnosis is essential to treatment. This is the first case of necrotizing GN (without extra-renal manifestations of vasculitis) in a patient with active RA, successfully treated with RTX.

Kidney stone (nephrolithiasis) is one of the most common diseases. During the past several decades, its prevalence and incidence have increased markedly in elderly population.
This study was conducted to evaluate the risk factors for nephrolithiasis in elderly population.
Patients and This study was based on the Amirkola Health and Ageing Project (AHAP). Elderly people with kidney stones in every size, type and number were considered to be the case group and other subjects without a history of kidney stones served as control group. Demographic and anthropometric data, smoking, diabetes and metabolic syndrome (MetS), calcium (Ca), vitamin D, parathyroid hormone (PTH), uric acid and urine pH were compared in both groups.
In this study, 1390 elderly people with the mean age of 69.37 ± 7.42 years were evaluated which 202 (14.53%) cases had renal stones. The patients with nephrolithiasis were younger (P = 0.010) and had higher uric acid and body mass index (BMI) levels (P = 0.041 and P = 0.006, respectively). Age This study suggests that male gender, obesity and age

Hemorrhagic shock (HS) is a condition produced by considerable loss of intravascular volume, which may eventually lead to organ damage and death.
In the present study, the potential implication of the kidney tissue tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were evaluated in the protective effects of erythropoietin (EPO) during HS.
Male Wistar rats were randomized into three experimental groups; Sham, HS (hemorrhagic shock and resuscitation), and EPO (erythropoietin). HS was induced by 50% blood volume hemorrhage over 30 minutes. After 2 hours, resuscitation was performed within 30 minutes. In the EPO group, EPO (300 IU/kg, i.v.) was administered 10 minutes before HS induction. Urine was collected to determine urinary N-acetyl-β-D-glucosaminidase (NAG) activity level. The kidney cytokines (TNF-α, IL-6 and IL-10) mRNA expressions were measured by real-time polymerase chain reaction (PCR).
HS rats showed significant increase in urinary NAG activity compared to the sham group. EPO significantly attenuated the rises in urinary NAG activity compared to the HS group. In the HS animals, renal TNF-α and IL-6 mRNA expressions increased whereas no difference was observed in IL-10 mRNA expression between the HS and sham groups. EPO was able to decrease renal TNF-α and IL-6 production and increase IL-10 mRNA expression.
In this study, we demonstrated that EPO attenuates kidney damage in rats subjected to HS. The beneficial effects of EPO may be at least partly mediated by modifications in the inflammatory cascade.

Free radicals production by toxicity of arsenic (Ar) is most important in the nephrotoxicity. There is accumulating evidence that zinc (Zn), has anti-oxidant properties.
The aim of present study was to evaluate protective and ameliorative effects of Zn against Ar-induced nephrotoxicity in rat pups during gestation and lactation.
Twenty-four adult pregnant wistar rats were randomly divided into four groups (n = 6). Group one was given vehicle only. Group two received Zn (ZnSO4) at 20 mg/kg/d. Group three received Ar at 5 mg/kg/d as sodium meta-arsenite. Group four received Ar Zn at the same dose that mentioned in groups of two and three. At the end of the study, 24 hours after the last treatment, samples were killed with overdose of sodium pentobarbital and kidneys were harvested for measuring malondialdehyde (MDA), glutathione (GSH) and histopathological assessment.
The MDA level in kidney was increased in the Ar group, which was decreased after Zn administration in the Ar  Zn group. The GSH level in kidney was decreased in the Ar group, which were increased after Zn administration in the Ar  Zn group. Also, the histopathological changes which were detected in the Ar group attenuated after Zn consumption.
Our findings suggested that administration of Zn during gestation and lactation could have protective and prevent effect in Ar-induced oxidative stress in kidney tissue.

Diabetes is the leading cause of end stage renal disease (ESRD) worldwide.
We compared the clinical outcomes in diabetic patients on hemodialysis (HD) with non-diabetics.
Patients and Adult maintenance HD patients (N= 532) from 9 HD facilities were enrolled to this prospective cohort study in September 2012. Causes of death, hospitalization, and HD exit were recorded in a median 28 months follow up period.
Results. Forty-one percent of patients were diabetic. Diabetic patients compared to non-diabetics had significantly higher age (62.2 ± 11.2 versus 53.1 ± 16.7 years), lower dialysis duration (median: 23 versus 30 months), more cardiovascular comorbidities (64% versus 28%) , higher C-reactive protein (CRP) levels (median: 3.80 versus 2.25 mg/L), lower serum albumin (3.86 ± 0.35 versus 3.93 ± 0.35 g/dL), lower intact parathyroid hormone (iPTH) (median: 272 versus 374 ρg/mL), higher serum triglyceride (167 ± 91 versus 139 ± 67 mg/dL) and low density lipoprotein (LDL) (82.5 ± 24.5 versus 77.5 ± 23.8 mg/dL), and worse short form health survey (SF36) score (45.7 ± 20.9 versus 52.7 ± 20.5). Annual admission rate was higher in diabetics (median: 0.86 versus 0.43) and diabetic foot involved 16% of their admissions. Transplantation rate was 4 and 9 per 100 patient years in diabetics and non-diabetics, respectively. Death rate was two folds higher in diabetics (24 versus 12 per 100 patient years). Cardiovascular diseases ( ± infections/other causes) comprised 80.5% of death in diabetics and 54.5% in non-diabetics. In Cox regression proportional hazard multivariate analysis, hazard risk of death in diabetics was 1.9 times higher than non-diabetics.
Clinical outcomes and health related quality of life (HRQOL) are much worse in diabetic compared to non-diabetic HD patients mainly due to more frequent of cardiovascular diseases (CVDs).

Mammalian target of rapamycin (mTOR) inhibitors are increasingly used as immunosuppressive agents in kidney transplantation. In the experimental setting it has been shown that mTOR inhibitors promote autophagy, but the concept that this might also occur in transplant patients has not been addressed.
This study was designed to investigate the association between mTOR inhibition and autophagy in renal transplants under routine clinical conditions.
Protocol transplant biopsies of patients receiving sirolimus were compared to biopsies of patients treated without mTOR inhibitor. Electron microscopy was used for quantitative stereological analysis of autophagosomal volume fractions. Ultrastructural analysis was focused on podocytes to avoid cell type bias. Autophagy-related gene products were profiled by QPCR from laser assisted microdissected glomeruli and by immunohistochemistry for semiquantitative evaluation.
By electron microscopy, we observed a significant > 50% increase in podocytic autophagosomal volume fractions in patients treated with sirolimus. Evaluation of biopsy material from the same patients using transcriptional profiling of laser capture microdissected glomeruli revealed no differences in autophagy-related gene expressions. Immunohistochemical evaluation of autophagic degradation product p62 was also unaltered whereas a significant increase was observed in podocytic LC3 positivity in biopsies of sirolimus treated patients.
These results indicate an association of sirolimus treatment and autophagosome formation in transplant patients. However, they might reflect autophagosomal buildup rather than increased autophagic flux. Further research is needed to investigate the potential functional consequences in short- and long-term outcome of patients treated with mTOR inhibitors.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) can be classified into; focal, crescentic, mixed and sclerotic classes. Macrophages and T lymphocytes are key players in mediating renal injury. The frequency of macrophage and T lymphocytes in different histological classes is unclear.
We examined the frequency of macrophage and T lymphocyte markers in AAGN and assessed their correlation with renal function at presentation.
Patients and Renal biopsies from 38 patients were included in immunohistochemistry analysis of macrophages (CD68, sialoadhesin [Sn] and mannose receptor [MR]) and T cells (CD4 and CD8) markers. The frequency of these markers in glomerular, periglomerular and interstitial compartments were measured in a blinded fashion. Biopsies were allocated a histological class of focal, crescentic, mixed or sclerotic. Scores were then matched to histological class and assessed for correlation with renal function.
The biopsies were crescentic 19 (50%), focal 10 (26.3%), mixed 6 (15.7%) and sclerotic 3 (8%). Interstitial CD68 macrophages and CD8 T lymphocytes showed best correlation with renal function at the time of presentation. CD68 macrophages were significantly increased in crescentic compared to focal AAGN. MR macrophages, CD4 and CD8 T cells were also elevated in the interstitium of crescentic compared to focal group.
In this study interstitial CD68 and CD8 showed the highest association with the renal function at presentation. Differences in the cellular infiltrate between focal and crescentic AAGN were related to CD68 macrophages and to interstitial MR macrophages and T lymphocytes. Further studies are needed to assess these differences across all four histological categories.