Journal of nephropathology
Volume:7 Issue: 3, Jul 2018

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder that affects the kidney in around 50% of patients
The aim of this study was to assess CD147 expression with various pathologic lesions, biochemical and demographic data in patients with classes III and IV lupus nephritis.
Patients and These patients with lupus nephritis classes II and IV by renal biopsy and pathology were enrolled in this study. The strength of CD147 staining on tubules, Bowman’s capsules, vessels and tuft of glomeruli was expressed as proportion of involvement.
In this study, 23 renal biopsies for lupus nephritis of classes III and IV (documented by immunofluorescence and light microscopic studies) were included. No significant difference of CD147 staining between classes was detected (P>0.05). In addition, proportion of proteinuria was not related to CD147 staining in tubules, Bowman’s capsules, vessels and tuft of glomeruli in classes III and IV lupus nephritis (P>0.05). There was no significant association of CD147 staining in tubules, Bowman’s capsules and vessels with serum creatinine (P>0.05). However, an association between CD147 staining in tuft of glomeruli with serum creatinine was detected (r=0.623, P=0.002). None of chronicity or activity percent of glomerular involvement in two classes of III or IV had a significant association with CD147 staining (P>0.05).
The significant association between CD147 staining in glomeruli with serum creatinine in lupus nephritis of classes III and IV revealed that inflammation at this area may have prognostic implication.

Context: There is mounting evidence suggesting bidirectional crosstalk between microbiota and host. However, the effects of probiotics on renal function and uremic toxins in chronic kidney disease (CKD) patients are unclear.
Evidence Acquisitions: A literature review was conducted using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through November 2017 to identify randomized controlled trials (RCTs) assessing the effects of probiotics on renal function and uremic toxins in CKD patients. Effect estimates from the individual studies were extracted and combined using fixed-effect meta-analysis with inverse variance weights.
Five RCTs with 161 CKD patients were enrolled. Compared to controls, there were no significant differences in serum creatinine and estimated glomerular filtration rate (eGFR) after post-probiotic course (4 weeks to 6 months) with standardized mean differences (SMDs) of 0.01 (95% CI -0.29 to 0.30) and -0.01 (95% CI -0.43 to 0.41), respectively. Compared to the controls, p-cresol levels were significantly reduced after treatment with probiotics with SMD of -0.61 (95% CI -1.04 to -0.19). No significant infectious complications were noted during treatment with probiotics in CKD patients.
Based on the findings of our meta-analysis, there are no significant changes in serum creatinine or eGFR after short-term treatment with probiotics, when compared to controls. However, our meta-analysis suggests potential beneficial effects of probiotics on uremic toxins in CKD patients. Future studies are required to assess its long-term effects on CKD progression and uremic toxins.

Kidney transplant is a fair option for treatment of a chronic renal failure. Although the outcome and results of kidney transplant are good, it may be associated with some complications. One of the important complications is urinary infection.
The aim of this study was to investigate the role of early removal of the catheter in renal transplant patients on the reduction of urinary tract infections.
Patients and This study was conducted as a clinical trial. Around 88 transplanted patients were enrolled and randomly divided into two groups. In the first group, the patients were taken 3 days after the transplant, and in the second group, patients were removed 7 days after the Foley catcher transplant. Urine culture was performed on two occasions. Then, the patients’ data were analyzed using SPSS version 20.
After examination of urine and analyzing the results with t test, it showed that infection of urine in the time of removal of urethral catheter was lower than 7 days after removing urethral catheter (P Early removal of catheter has fundamental effects on UTI after kidney transplant and it seems that early removal of urethral catheter may be safe and reasonable in renal transplant of the recipient patient.

Context: In normal conditions, liver and kidney act as a supply of internal antioxidants for neutralizing free radicals produced by viruses and internal/external compounds which were processed in the liver and kidney.
Evidence Acquisition: PubMed, EBSCO, Embase, Web of Science, directory of open access journals (DOAJ), Scopus, and Google Scholar were searched using keywords of oxidative stress, free radicals, liver diseases, kidney diseases and antioxidant therapy.
When the antioxidants of the liver or kidney are low, or when the liver/kidney is under pressure through oxidative insults, the damages produced by free radicals would increase, leading to inflammation and fibrosis. In addition to cytotoxic effect of oxidative stress, it has also a substantial role in modulating of messengers in regulating the functions of cell membrane, with a vital factor for survival. However, there is also some benefits of oxidative stress such as inducing apoptosis to prepare birth canal for delivery or strengthening of biological defense mechanisms during ischemia and physical exercise.
There is an important association between diseases related to lifestyle and oxidative stress, as a condition that oxidation may exceed the antioxidant systems of the body with absence of balance between them. Oxidative stress is involved with many diseases such as kidney, liver and lung dysfunctions. Supplementation with vitamins C and E and selenium for four months could improve the balance between antioxidant-oxidant as well as potential slowing down of liver disease progression.

Context: The prevalence of diabetes markedly increased in recent decades. It is well accepted that the risk of morbidity and fatality increases in patients with type 2 diabetes (T2DM).
Evidence Acquisition: An electronic search was performed to detect suitable studies, with keywords of metformin, prediabetes, diabetes Mellitus, Gentamicin and lactic acidosis.
Metformin (biguanide) is widely used as the first pharmacological option in pre-diabetic subjects and patients with T2DM. Low-cost, long-term effect, low risk of hypoglycemia, and ease in utilization are considered as significant benefits of metformin compared with other therapies. Numerous studies have explored that medicinal intervention particularly metformin administration not only can decrease high blood glucose in patients with T2DM but also can avoid or postpone the beginning of clinical T2DM in pre-diabetic cases. Protective effect of metformin on renal cells by different mechanisms is described here. Gentamicin is an important factor that affects kidney function and structure. Nephrotoxicity is one of the serious side effects of gentamicin (an aminoglycoside antibiotic). Numerous investigation showed the protective effect of metformin against the gentamicin nephrotoxicity. On the other hand, lactic acidosis is known as an uncommon but serious side effect of metformin that should be mentioned. Signs of lactic acidosis are defined by plasma lactate levels higher than 5 mmol/L and pH smaller than 7.4.
Different small series and large experimental investigations have discovered the association between metformin and lactic acidosis summarized here.

Context: Hypertension is one of the most important issues in advanced and developing countries and is prevalent in diabetic patients. The present study was aimed at estimating the prevalence of hypertension in diabetic patients in Iran through meta-analysis.
Evidence Acquisitions: The search was carried out using authentic Persian and English keywords in national and international databases including IranMedex, SID, Magiran, IranDoc, Medlib, ScienceDirect, PubMed, Scopus, Cochrane, Embase, Web of Science, Medline and Google Scholar search engine without any time limitation until 2017. Heterogeneity of studies was assessed using I2 indexes. Data were analyzed using STATA software version 11.1.
In 32 reviewed studies with a sample of 34714 subjects, the prevalence of hypertension in Iranian diabetic patients was 51% (95% CI, 43%-60%). The prevalence of hypertension was 55% in type I diabetics and 53% in type II diabetic patients. Metaregression showed that there was no significant relationship between the prevalence of hypertension in diabetic patients with the sample size and year of study.
About half of the diabetic patients in Iran suffer from hypertension. Patients with type 1 diabetes suffer from hypertension 2% more than type 2 diabetes patients. The prevalence of hypertension in diabetic patients in Iran has not significantly decreased over the past years and diabetic patients in northern Iran are more likely to have hypertension than other parts of the country

Contrast-induced acute kidney injury (CI-AKI) is one of the possible complications in angiography, which its prevention is important. N-acetylcysteine is one of the compounds that has recently been more investigated regarding its effect on CI-AKI.
The aim of this study was to investigate the effect of standard dose and twice-thestandard of N-acetyl cysteine on prevention of contrast-induced nephropathy.
Patients and In a clinical trial, 154 individuals who were referred for angiography and had glomerular filtration rate (GFR) ≤60 mL/min, enrolled in and randomly divided into two groups. Group A received the usual dose of N-acetyl cysteine and group B received twice the standard. Blood urea nitrogen (BUN), creatinine, and GFR values were measured and recorded at intervals before, 24, 48 and 72 hours after angiography. Other required laboratory parameters were also measured and recorded.
The results of this study indicated that the effect of double dose in males and females is not different. It also has a reverse effect on renal function in older patients. Its effect did not differ in diabetic patients compared to non-diabetic patients. N-acetyl cysteine in dose of twice the standard has not any effect on renal function in patients with hyperlipidemia, hypertension, myocardial infarction, pulmonary edema as well as smoker patients. In patients with congestive heart failure (CHF), N-acetyl cysteine in dose of twice the standard had a positive effect on renal function compared with those who did not have CHF. An interesting point in our study was the negative effect of N-acetyl cysteine in dose of twice-the-standard on renal function in patients with lower hemoglobin and hematocrit levels.
Our study showed that an increase in the dose of N-acetyl cysteine is not effective in preventing contrast-induced nephropathy and improving renal function. Of course, in some groups, such as those with CHF, a positive effect was detected. Additionally, in some groups including patients with lower hematocrit and hemoglobin, an increase in dose is associated with a negative effect on renal function.

ABO-incompatible (ABOi) kidney transplantation can be achieved by desensitizing the recipient using apheresis plus rituximab-based immunosuppression.
We sought to ascertain the factors that contributed to low immunoglobulin levels at post-ABOi kidney transplantation.
Patients and This single-center study included 43 ABO-i kidney-transplant recipients desensitized with rituximab-based therapy. Posttransplant immunoglobulin levels (IgG, IgA, and IgM) were prospectively monitored within 2 years. If severe hypogammaglobulinemia occurred, i.e., IgG levels Within 1-year posttransplantation, 25% of patients experienced at least once severe hypogammaglobulinemia. On D –30 (pre-transplantation), IgG, IgA, and IgM levels were within normal ranges: 10 ± 4.4, 1.9 ± 1.2, and 0.8± 0.5 g/L, respectively. IgG levels were significantly decreased at D0 (4.2 ± 3.8 g/L) compared to D–30. At D15, IgG levels did not significantly differ from those on D0 or D –30. Conversely, beyond month-1 posttransplant IgG levels were within normal ranges and were significantly higher than levels measured on D0. Within three months posttransplantation, 11 patients required IVIg because IgG levels were We conclude that hypogammaglobulinemia occurred frequently after ABOincompatible kidney transplantation but did not cause more infectious complications.

The use of zinc oxide nanoparticles (ZNPs) in various products such as biosensors, sunscreens and nourishment added substances is increasing.
In the present work the impacts of ZNP on kidney of rats was explored.
In this experimental study male Wistar rats were used. Trial groups received 5, 50 and 300 mg/kg ZNP (ZNP-1 to ZNP-3) for 2 weeks. Control group received only normal saline. blood urea nitrogen (BUN), creatinine (Cr) and uric acid were considered as biomarkers to indicate nephrotoxicity. To evaluate the oxidative stress in the kidney, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzymes activity were measured. Histopathological and apoptotic cell death was also evaluated in renal tissues.
Blood density of zinc (Zn) was significantly increased in the low dose-treated rats. Concentration of Zn in the renal tissue was significantly increased in the high dose treated rats. Weight of kidney was significantly elevated in both ZNP-1 and ZNP-2 groups. ZNP resulted in a significant increment in MDA content in the low measurements and a critical reduction in the activity of the SOD and GPx enzymes. Exposure of ZNP at low dose induced a significant elevation in blood concentration of BUN, Cr and uric acid. Treatment with low dose of ZNP caused a significant increase in histological changes and apoptotic index. ZNP at the high dose induced poor nephrotoxicity.
In conclusion, ZNP has dose-dependent nephrotoxic effects on rats and lower doses have more toxic action.

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). Activation of complement system which leads to the production of C4 and its ultimate product, C4d, plays an important role in the pathogenesis of LN.
Although serum C4d levels correlate with disease activity, there is almost no study on the correlation between tissue deposition of C4d and classes of LN.
Patients and Seventy-two patients with a diagnosis of SLE who met ≥ 4 criteria of American Rheumatism Association (ARA) were enrolled in this study. Blood levels of anti-nuclear antigens (ANA), anti-double stranded DNA (Anti-dsDNA), C3, C4 and antiphospholipid antibodies were measured. Renal tissue obtained by biopsy was examined regarding diffuse granular deposition of C4d along the glomerular capillary loops and classes of LN according to the World Health Organization (WHO) classification.
LN class IV was the most prevalent and LN class I had the least prevalence. There was no correlation between positive C4d staining and classes of LN (P>0.05), but a significant correlation between positive Anti-dsDNA and C4d positive LN was found (P=0.05). Likewise no correlation was detected between the low levels of complements and classes of LN or C4d positivity.
The presence of C4d indicates activation of classical complement pathway in LN. C4d deposition in glomerular capillaries of LN does not indicate the present disease activity but may be a useful marker to predict the prognosis of LN. Anti-dsDNA is a valuable test for disease activity and is correlated with C4d positive staining.

Oxidative stress and impaired antioxidant capacity in diabetes are associated with diabetic nephropathy. Metformin, as an adjunct to insulin could decrease oxidative stress and may therefore improve renal function in type 1 diabetes (T1D).
To investigate the effects of metformin as adds-on therapy to insulin on renal dysfunction in T1D.
Male Sprague-Dawley rats (230-250 g) were divided into 5 groups (n =7). Rats in groups A and B were orally treated with 3.0 mL/kg body weight (BW) of distilled water, while those in groups C and D were treated with insulin (4.0 U/kg BW bid) or oral metformin (250 mg/kg BW), respectively. Group E rats were similarly treated with both metformin and insulin. Groups B-E were rendered diabetic by intraperitoneal injections of 65 mg/kg BW of streptozotocin. Fasting blood glucose concentrations and glucose tolerance tests were done. The animals were sacrificed by halothane overdose after 56 days, blood taken by cardiac puncture and kidneys excised and stored at -80°C for further analysis.
Untreated diabetic rats exhibited significant weight loss, increased polydipsia and polyuria, impaired glucose tolerance, electrolyte retention, reduced creatinine clearance and urea excretion and increased oxidative stress compared to controls, respectively. However, these were reversed by treatment with metformin and insulin.
Metformin does not improve glycemic control in TID but exerts renoprotective effects by reducing oxidative stress in the presence of insulin. Metformin should therefore be considered for adjunct therapy with insulin in TID.

Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome that presents with proteinuria, usually in the nephrotic range and evidence of histologic lesions of focal and segmental glomerular sclerosis with diffuse foot-process effacement. Recently, suPAR (soluble urokinase-type plasminogen activator receptor) was proposed as the potential circulating causative factor for primary FSGS.
We performed a cross-sectional study with the aim to determine whether there is a relationship between suPAR serum levels and primary FSGS. The secondary aim was to associate serum suPAR levels with kidney dysfunction.
Patients and We enrolled a total of 90 patients with both suPAR serum levels and proteinuria. From these, 61 patients performed a renal biopsy.
The mean age was 49.8±17.2 years, 37 was females (60.7%) and 54 were Caucasian race (91.5%). FSGS was diagnosed in 30 patients (49%). suPAR levels were positive in 34 patients (55.7%) and negative in 27 (44.3%). Concerning the positive results, 17 patients had the histologic diagnosis of FSGS, which gives the test a sensibility of 28%. Concerning the negative results, 14 patients had a different histologic diagnosis other than FSGS, which gives the test a specificity of 23%. The predicted positive value was 50% and the predicted negative value was 52%. suPAR serum levels were not correlated with 24 hours proteinuria (P=0.5), but we found a positive correlation with C-reactive protein (P=0.037) and an inverse correlation with estimated glomerular filtration rate (eGFR) (P We found that a positive suPAR test is not a marker of FSGS, but it can be a marker of podocyte and glomerular lesion, as it is inversely correlated with renal function in a cohort of proteinuric patients. Further studies are needed to further validate suPAR as a specific biomarker of glomerular damage.

Pediatric patients with steroid-resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) may relapse and current second line agents include mycophenolate mofetil. However, there is no current information about the use of the sodium salt of mycophenolic acid (SMPA) in this population.
We conducted a prospective study on the efficacy and pharmacokinetics of SMPA in children with FSGS.
Patients and Patients without NPHS2 pathogenic variants received SMPA at dosages between 460 to 720 mg/m2/d for 12 months after previous treatments failure. Clinical and biochemical assessments were performed. Blood samples were obtained after the first dose and at steady state (3 months after the onset of treatment) and total and free mycophenolic acid (MPA) was quantitated using HPLC-UV.
Two patients showed partial remission after the 12-month period of SMPA treatment with a notable decrease in proteinuria and an increase in serum albumin levels. Maximum MPA concentrations after the first dose and at steady state were 11.6 µg/mL and 10.5 µg/mL, respectively, without drug accumulation. Maximum MPA free levels after the first dose and at steady state were 192.9 and 120.6 ng/mL, respectively. MPA levels became undetectable after 4 hours of the administration in all cases.
SMPA is a promising agent for pediatric patients with SRNS and FSGS but SMPA schedule of treatment should be revised with shorter intervals of administration and higher doses than those used in the present study in order to attain higher systemic exposures and accumulation of the immunosuppressant drug. Further efficacy and pharmacokinetic studies should be performed to confirm these findings.

Iron deficiency anemia is common in patients on maintenance hemodialysis (HD). Serum ferritin is increased in HD patients. Vitamin C supplementation has shown to improve functional iron deficiency and anemia in HD patients.
In this study we aimed to evaluate the effect of vitamin C supplementation on serum ferritin level.
Patients and In this randomized clinical trial, 39 HD patients were randomly assigned to receive routine therapy with (n=24) or without (n=15) vitamin C 500 mg IV twice a week after each dialysis session for 2 months. Changes in serum ferritin, iron, total iron-binding capacity (TIBC) and transferrin saturation (TS) before and after treatment were measured in each group.
Serum ferritin levels before treatment in case and control groups were 1859±1398.5 and 2567.5±1907.8 ng/mL which was significantly decreased to 1084.8±727.9 and 1313.5±1151.5 ng/mL, respectively (P=0.006 and P=0.007). Serum iron, TIBC and TS did not change significantly in each group after treatment. Comparing the mean changes in serum ferritin, iron, TIBC and TS, there was no significant difference between groups.
Vitamin C had no effects on serum ferritin, iron and TS.

Obstructive sleep apnea (OSA) occurs frequently in hemodialysis (HD) patients with important consequences and increased mortality. However the role of adequacy of HD on the prevalence of OSA is less studied.
Our aim was to screen OSA and evaluate the effect of HD adequacy on the risk of OSA.
Patients and This is a cross-sectional study on adult HD patients. Clinical and laboratory parameters were collected. The risk of OSA was assessed by STOP-BANG and Berlin questionnaire (BQ). Excessive daytime sleepiness (EDS) was evaluated with Epworth Sleepiness Scale (ESS). Kt/V index was applied for determining HD adequacy. Mortality followed after 2 years.
Sixty-five patients (63% men, with a mean age of 53±16.5 years) were included in the study. Most of the subjects were categorized as high risk by Berlin (68.3%) and STOPBANG (84.6%) questionnaires and 25.8% had EDS. Participants who were categorized as high risk of OSA showed lower Kt/V (P=0.018 based on BQ, P=0.002 based on STOPBANG). OSA risk was significantly correlated with Kt/V (OR: 0.007; CI: 0-0.36; p: 0.01). Two-year mortality was not significantly correlated with OSA.
OSA was prevalent in our HD patients and correlated with less adequacy of HD. Screening for this common disease by nephrologists using simple questionnaires is recommended.

Guillain-Barré syndrome (GBS) is an autoimmune disease damaging the peripheral nervous system. It commonly presents as rapidly progressing bilateral symmetrical motor weakness. There has been known association of syndrome of inappropriate antidiuretic hormone (SIADH) in patients with GBS though it is rare.
We report a patient with rare clinical presentation of SIADH before the onset of motor deficits in GBS.
SIADH as an initial finding in patients with GBS is very rare. This case report emphasizes the importance of early detection of SIADH in GBS to avoid delay in treatment.

Renal complication in hypereosinophilic syndrome (HES) is rare, with literature scarcely reporting association of this syndrome with glomerular involvement. While the direct effect of eosinophilic infiltration in tissues has been linked to histological damage of the HES, other mechanisms may account for renal involvement too.
We present a case of a 17-year-old male patient, with progressive edema, contact reactive erythematous skin lesions, acute kidney injury, nephrotic syndrome and progressive eosinophilia. His bone marrow biopsy revealed moderate hyperplasia with severe eosinophilia and atypical lymphocytes. His renal biopsy revealed glomeruli, enlarged in volume with mesangial expansion and hypercellularity and segmental thickening of capillary loops. Likewise, some glomeruli showed peripheral hyalinosis with synechiae to Bowman’s capsule. Tubules showed cloudy swelling, mild tubular atrophy and hyaline cylinders. Interstitial area showed infiltrated lymphomononuclear cells, focal with no evidence of eosinophils. Blood vessels were unaltered. Immunofluorescence identified glomeruli with granular mesangial IgM deposition. After corticosteroid treatment, eosinophilia and creatinine values regress to normal range.
While our case may suggest the coexistence of two unrelated diseases, further studies are required to assess the pathophysiology of glomerular involvement in HES. Given the possibility that mechanisms other than the direct effect of eosinophils are involved in certain patients

The majority of Leydig cell tumors (LCTs) are found in males, usually when they have 5–10 years of age. Children typically present with precocious puberty due to excessive testosterone secreted by the tumor, one-third of female patients present a recent history of progressive masculinization. Alkaline phosphatase is normally at low levels.
A 30-year-old male referred to the hospital with a complaint of fever, chills, nausea and weight loss, and history of diabetes mellitus type 1. In the physical examination of testis, no abnormal findings were revealed. Scrotal ultrasonography demonstrated a small (7.5 ×4.8 mm) mass which seemed to be very vascular and suggestive of neoplastic lesion. Echogenicity of the head of the right epididymis was heterogeneous and the small cyst of about 4.5 mm was present on it. Left testis had normal size and no space occupying lesion in it. The hormonal test revealed high levels of alkaline phosphatase, ferritin, FSH and LH, normal level of testosterone, LDH, β-HCG and α-feto-protein. Immunohistochemistry results revealed negative CD30, alpha-fetoprotein and CK results, but calretinin, vimentin and S-100 were positive in tumor cells.
LCTs are rare testicular tumors arising from male gonadal interstitium and very rare in adulthood. Because this tumor consists of immature embryonic tissues it can be accompanied by an elevation in alkaline phosphatase level.