Journal of nephropathology
Volume:8 Issue: 2, Apr 2019

The current treatment regimens for patients with idiopathic membranous nephropathy (MN) are based on cyclophosphamide-glucocorticoid or calcineurin inhibitor-glucocorticoid. We evaluated whether mycophenolate mofetil (MMF) -glucocorticoid could be an option for first-line therapy among these patients. In a double-blinded, randomized and controlled clinical trial, we compared the effect of MMF with cyclophosphamide in inducing complete or partial remission (PR) among patients with nephrotic syndrome due to idiopathic MN. All of the patients in both groups also received steroid, renin-angiotensin blockers and statins. Diuretics were also used in the patients who had edema. The primary end point of our study was change in urinary protein/creatinine ratio. A total of 30 patients completed the study. Around 17 patients received MMF (2 g/d) and 13 patients received intravenous or oral cyclophosphamide for 6 months. At the start of the study, no significant differences in demographic and biochemical parameters of patients including the urinary protein excretion rate between two groups (P = 0.432). The proportion of proteinuria was 5235 ± 1655 mg/24 in MMF group and 8781 ± 8741 mg/24 in the cyclophosphamide group at the beginning of the study. The rate of complete and PR were 5.9% and 52.9 in MMF group versus 16.7% and 100% in cyclophosphamide group which it is significantly lower in MMF group. Kidney function was stable in both groups during treatment. According to the result of our study, a 6-month therapy with MMF-glucocorticoid is not recommended for treatment of patients with nephrotic syndrome due to idiopathic MN.

Chronic kidney disease (CKD) and uremic syndrome cause malfunction in most of organs including skin. This study was designed to investigate the effects of omega-3 supplement on uremic pruritus in chronic hemodialysis patients. In this double-blind randomized controlled clinical trial study (#IRCT cod; 29363; http://irct.ir/trial/29363), the effect of the omega-3 supplement on uremic pruritus was assessed in 64 chronic hemodialysis patients (using standard 5-D itch scale questionnaire). Patients were surveyed at the hemodialysis department of Imam Khomeini and Razi hospitals in Ahvaz city, Iran. We found that the mean score of itching degree in the intervention and the placebo groups decreased from 3.56 to 1.72 (P<0.001) and 3.63 to 3.09 (P<0.05) respectively. In our study, the omega-3 supplement could reduce uremic pruritus in chronic hemodialysis patients.

Coronary artery disease (CAD) is the first cause of mortality in developed and developing countries, including Iran. Identifying high-risk patients can save many from morbidity and mortality. Renal artery stenosis (RAS) seems to be equivalent to CAD in patients with cardiovascular risk. The present study aimed to determine the prevalence, severity, and extent of RAS and its predictors in patients with confirmed CAD on coronary angiography. All patients suspected of ischemic heart disease (IHD), who underwent diagnostic coronary angiography at Heshmat heart hospital, Iran were recruited (May 2015 to June 2016). Patients with confirmed CAD underwent non-selective renal angiography, which was categorized as mild, moderate or severe based on luminal diameter narrowing more than normal >0% to 50%, between 50%-70% and more than 70%, respectively. Of 233 patients, RAS was observed in 123 (53%). Around 20% were mild, 10% were moderate and 23% were severe. Additionally, RAS in 37% was unilateral and in 16% were bilateral. Besides,19%, 25% and 56% of patients had atherosclerosis in one, two and three vessels, respectively. There was no correlation between the CAD severity and severity of RAS (P=0.807). Higher prevalence of RAS in patients with hyperlipidemia (60% vs. 40%) was detected. Its association with variables affecting CAD indicates that RAS can be a predictor of CAD. Therefore, simultaneous assessment of RAS in coronary angiography can be a good screening method for CAD beside earlier diagnosis of kidney disease.

BK polyomavirus is a member of the Polyomaviridae. This virus has spread worldwide and up to 82% of the world populations are serologically positive. BK polyomavirus usually transmits through inhalation or fecal-oral way in childhood, as well as is likely to cause an asymptomatic disease. The virus can be reactivated in people who are immunocompromised. In this study we aimed to determine the complete genome sequence of BK polyomavirus in 5 patients receiving kidney transplantation in Golestan hospital, Ahvaz, south west of Iran. The study was performed on urine and blood samples from kidney transplant ward, Golestan hospital, Ahvaz, Iran. To amplify the whole genome of BK polyomavirus AccuPower ProFi Taq PCR PreMix kit (Bioneer, South Korea) was used. Then, purified fragments were cloned into the vector. Sequences derived from the sequencing process were assembled by MEGA7 software. Data were analyzed using MEGA7 software and a phylogenetic tree was built based on the maximum likelihood ratio method. Overall, 40 urine samples (40%) and two plasma samples (12%) were positive for BK virus DNA. For the selected samples, W.G. Long PCR was performed and 5.1 kbp fragment was observed in all five samples. These fragments were cloned and sequenced. Genomic sequence analysis of the 5 strains studied showed 97.6% homology and all our study samples were of the same clade, which could be a reason for our patients to be infected with the same strain. Comparing the 5 isolates in our study with reference strains, showed more than 98% of homology, and variation was observed in less than 2% of nucleotides. These five isolates showed more than 98% homology compared to the reference sequences, which can be attributed to the fact that these patients are infected with a common strain or that the genomic stability in the strain exists in our geographic area. We can conclude that in our geographic region there is a genomic stability and this strain can also be used as a positive control sample in other parts of the country

Nephrotoxicity is the most known side effect of gentamicin. In addition, renin angiotensin system (RAS) plays an important role in the pathogenesis of renal injury and nephrotoxicity. Hypomagnesaemia is other complication of gentamicin. Previous studies reported that magnesium plays an important role in cell enzymatic functions, reducing lipid peroxidation. We investigated the role of losartan and magnesium sulfate (MgSO4 ) on gentamicin nephrotoxicity. In this study, rats randomly assigned to five groups. The first group, received saline, the second group received gentamicin 80 mg/kg/d, intraperitoneally (ip), and the third group, received a regular dose of losartan, 10 mg/kg/d + gentamicin 80 mg/kg/d. The fourth group received MgSO4 , 80 mg/kg/d + gentamicin 80 mg/kg/d. The fifth group obtained a continuous dose of gentamicin 80 mg/kg/d + losartan 10 mg/kg/d + MgSO4 80 mg/kg/d simultaneously. Nine days after administration of drugs, blood samples were collected from the heart. The level of urea, creatinine (Cr), malondialdehyde (MDA) and nitrite were measured in the animal serum and homogenized kidney tissue. Gentamicin increased serum urea and Cr levels. The administration of losartan and MgSO4 lonely and combination of them, significantly reduced the levels of serum urea and Cr. Losartan alone and combination of losartan and MgSO4 compared with gentamicin, significantly decreased kidney MDA level too. Decrease of kidney nitrite level by gentamicin was compensated by the administration of losartan, MgSO4 alone or their combination. Additionally, losartan and MgSO4 alone and their combination together significantly reduced renal damage. The results of this study indicated that administration of losartan and MgSO4 individually and their combination decreased kidney nephrotoxicity and improved renal function. This effect is probably related to the improvement of antioxidant status and renal blood flow.

Cardiovascular disease (CVD) is prevalent among patients with chronic kidney disease (CKD) and its occurrence and severity cannot be fully defined by the conventional cardiovascular risk factors namely age, hypertension, dyslipidaemia, diabetes mellitus and obesity. Contemporary studies have examined the role of non-conventional risk factors such as anemia, hyperhomocysteinemia, calcium and phosphate metabolism, vascular stiffness due to endothelial dysfunction ( ED), oxidative injury, and inflammation in the causation of CVD in CKD. Therapeutic interventions used in non-CKD patients are found to be less effective on patients with CKD. The purpose of this review was to gather available evidence on the CVD risk among CKD patients. Numerous mechanisms have been postulated to describe the increased atherogenicity in CKD patients. We discuss these mechanisms especially arterial stiffness, ED and inflammation in detail. In conclusion, CVD in CKD is still an unexplored area which needs further studies to uncover the possible mechanisms. Identifying newer therapies to improve health among this group of patients is of paramount importance.

 Mitochondria play a vital role in producing the energy needed for different cellular activities. The role of mitochondria in different diseases and the aging process is gradually being clarified. Different studies have suggested that mitochondrial dysfunction due to mutations in genes that maintain the integrity of mitochondrial DNA (mtDNA), mitophagy, and apoptosis can lead to many neurological and muscular phenotypes as well as diseases in other organ systems including liver, gastrointestinal tract, heart, and kidneys. We examined the current knowledge of mitochondrial dysfunction and its role in renal pathophysiology. Additionally, we examined how chronic kidney diseases can lead to mitochondrial dysfunction through oxidative stress accumulation, which can subsequently lead to other pathological complications.  Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO), and Web of Science have been searched. The renal pathological manifestation of mitochondrial dysfunction includes tubular defects, focal segmental glomerular sclerosis (FSGS), glomerular dysfunction, interstitial nephritis, and cystic kidney disease or renal tumors. These conditions can be caused by mutations in the nuclear genes that are involved in mtDNA replication and transcription or due to mtDNA mutations in the genes involved in the respiratory chain. Clearly, mtDNA plays an important role in renal pathology, and mitochondria may serve as a potential therapeutic target to treat different renal pathologies.

Calciphylaxis is a potentially fatal condition previously observed in patients with poor renal function. We present a case of atypical presentation in a patient with good renal function after transplantation. A-68-year old African American female with history of end-stage renal disease (ESRD) secondary to type II diabetes mellitus on hemodialysis for ten years, status post living related donor kidney transplant from her son three years prior to this presentation, parathyroidectomy, and atrial fibrillation on warfarin presented to our institution with progressively worsening, severely tender bilateral thigh lesions that were diagnosed as calciphylaxis. She was treated with sodium thiosulfate infusions for six months and continues to do well. Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), has traditionally been associated with ESRD patients on maintenance dialysis, however several nonuremic cases of CUA have been reported in recent years. Multiple pathophysiologic mechanisms for CUA development have been proposed expanding the scope of known risk factors and possible triggers. CUA can be a life-threatening condition that is important for clinicians to recognize and treat as soon as possible.

Castleman disease (CD) is a rare and heterogeneous lymphoproliferative disorder with a wide variety of clinical presentations and outcomes. Human herpesvirus-8 (HHV-8) related CD corresponds to the most common subtype of the multicentric Castleman disease (MCD). However, if HHV-8 is negative, POEMS (peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) associated with MCD or idiopathic MCD are the cause in a subgroup of patients. Considering the rarity of POEMS and MCD association, we herein describe a patient with a typical presentation based on clinical, laboratory and tissue biopsy data. We report a diabetic patient who presented with asthenia, edema, skin lesions manifested by scarring in chiropodactyls, multiple lymph node enlargement in the neck, armpits and inguinal areas, splenomegaly, severe anemia, thrombocytopenia, and mixed polyneuropathy. Hematuria and proteinuria were detected. The patient developed progressive renal failure requiring dialysis. Renal biopsy showed mesangial expansion with mesangial hypercellularity, and lymphoplasmacytoid cells focally distributed in tubules and interstitium, which were compatible with acute tubulointerstitial nephritis. In immunofluorescence, no deposits of IgG, IgA, IgM, C1q, C3 or fibrinogen were found, and kappa and lambda were also negative. Lymph node biopsy revealed lymphoid tissue with follicular hyperplasia, sinusoidal and medullary infiltration of plasma cells. Immunohistochemistry confirmed positivity for B lymphocytes, T lymphocytes, and plasma cells in sub-capsular and para-follicular areas. The patient was diagnosed as POEMS-associated MCD variant, and chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone was started. The patient did not recover renal function and remained dialysis-dependent. To date, the renal involvement in MCD and POEMS syndrome seems to be uncommon as reported in few case series. Its pathophysiology is not well understood. In the spectrum of MCD, decreased renal function may have impact in patient survival. Early diagnosis and treatment are needed to control the systemic manifestations, and most importantly to avoid chronic organ damage