Iranian Journal of Kidney Diseases
Volume:9 Issue: 4, Jul 2015

Endoplasmic reticulum produces folds and exports proteins. There are studies showing the role of endoplasmic reticulum in pathogenesis of diabetic complications including diabetic nephropathy. This article reviews the pathophysiology associated with the role of endoplasmic reticulum in diabetic nephropathy and the therapeutic aspects of this finding.

Shortage of deceased donor kidneys has resulted in an increased rate of kidney transplantation from living unrelated donors (LURDs). However, there are concerns about short-term and long-term morbidity of the donors. This study reports the clinical and biochemical factors in a follow-up program of Iranian LURDs, one of the largest reported series of kidney donors. Of 7500 individuals who underwent living donor nephrectomies between 2005 and 2008, a total of 1549 participated in this study. They were followed for 18 to 48 months after the kidney donation. The average time for the first study visit was 316.72 days after donation. The mean age of donors was 30.43 ± 6.16 years old. Men consisted 82.5% of the group. Systolic hypertension was detected in 0.2% and diastolic hypertension in 1% of the LURDs; however, anemia prevalence was as high as 47.2%. Hyperuricemia was found in 21.2% of the LURDs, while proteinuria was seen in 13.7%. Glomerular filtration rate was greater than 90 mL/min in 38.2% of the donors, 60 mL/min to 90 mL/min in 54.5%, and less than 60 mL/min in 7.3%. A GFR less than 45 mL/min was seen in 0.1% of the donors. Data suggested that the LURDs in Iran have an appropriate health condition comparable to other donors in other parts of the world. Considering the high prevalence of hyperuricemia in our population and its importance as a risk factor for kidney failure, monitoring serum uric acid in follow-up programs is suggested.

C1q nephropathy is a relatively rare idiopathic glomerulopathy characterized by mesangial immunoglobulin and complement deposits with dominance or co-dominance of C1q, with no evidence of systemic lupus erythematosus. We describe the incidence, clinical manifestation, histopathological features, and follow-up of patients with C1q nephropathy at our institute. Of 750 kidney biopsy specimens obtained in the period of January 2000 to December 2011, all the cases that meet the criteria for the diagnosis of C1q nephropathy were retrieved. The histological slides were examined and the clinical charts were reviewed by 2renal pathologists. We had 11 patients, all children, that met the criteria for the diagnosis of C1q nephropathy accounting for an incidence of 1.5%. The mean age at the time of presentation was 3.7 years and all the patients were presented with nephrotic syndrome. Two patients had microhematuria and 2 had hypertension. Histological examination of these cases showed variable degrees of mesangial cells hypercellularity and matrix expansion with focal segmental glomerulosclerosis observed in 2 cases. Nine patients were steroid resistant (82%) and 2 were steroid dependent. Six patients required immunosuppressive therapy and 1 patient developed end-stage renal disease. In our series, C1q nephropathy affected predominantly young children. Mesangioproliferative pattern was the most frequent histopathological finding in these patients. Clinically, despite steroid resistance, the patients had a relatively good outcome; the worst prognostic outcome was associated with collapsing glomerulopathy.

This study aimed to determine diagnostic value of immunoperoxidase in comparison with immunofluorescence in the diagnostic assessment of kidney biopsy specimens. Forty-eight kidney biopsy specimens were used to compare a direct immunofluorescence technique with immunoperoxidase techniques on paraffin sections. The sensitivity and specificity were calculated. The kappa statistic for agreement between the two tests was categorized as poor (zero to 0.2), moderate (0.21 to 0.45), good (0.46 to 0.75), and almost perfect concordance (0.76 to 1.0). Compared with immunofluorescence, the immunoperoxidase technique presented a sensitivity of 88.55% and a specificity of 69.22%. Its sensitivity in the staining for IgG, IgM, and IgA was 93.75%, 95.45%, and 76.47%, respectively. The specificity of this test in the staining for IgG, IgM, and IgA was 54.54%, 57.14%, and 96.00%, respectively. The overall kappa value was 0.60 and it was 0.60 for assessing staining intensity. There was a moderate agreement between immunoperoxidase and immunofluorescence in the positive or negative staining for IgG and IgM, as well as a good agreement in the positive or negative staining for IgA. For the staining intensity, the two tests had a good concordance for IgG and IgA and a moderate concordance for IgM. Although immunoperoxidase method has a lower overall diagnostic performance as compared to immunofluorescence, given the good concordance between the two techniques, it can be an alternative method for immunofluorescence study of kidney biopsy specimens, particularly where immunofluorescence fails or is not available.

Expression of Klotho is decreased and endoplasmic reticulum (ER) stress is activated in patients with chronic kidney disease. This study aimed to investigate the effect of Klotho protein on ER stress-related apoptosis and renal fibrosis in rates with unilateral ureteral obstruction (UUO). Twenty-four rats were divided into the sham, UUO, and Klotho treatment groups. Renal interstitial fibrosis model was induced by UUO in the rats of the latter two groups. Soluble Klotho protein was injected into the abdominal cavity. Serum and kidney samples were collected 14 days after the UUO surgery for examination of renal injury and renal interstitial fibrosis using hematoxylin-eosin and Masson trichrome staining methods. The level of apoptotic cells was assessed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Expression of 3 ER stress-related proteins including glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, and caspase-12 were measured. Kidney dysfunction, increased renal injury index, and aggravated renal fibrosis were documented in the UUO group. Expression of Klotho in the UUO rats was remarkably decreased (P <. 05) and expression of all three ER stress-related proteins were significantly upregulated, accompanied by increasing numbers of apoptotic cells (P <. 05). Soluble Klotho administration improved kidney function, ameliorated pathological changes, decreased expressions of ER-stress related-proteins, and reduced the number of apoptotic cells. Unilateral ureteral obstruction decreased Klotho expression and activated ER stress and related apoptosis. Klotho administration ameliorated UUO-induced ER stress, inhibited apoptotic process, and attenuated renal fibrosis.

A higher incidence of allergic disorders has been documented in children with steroid-sensitive nephrotic syndrome (SSNS); however, the role of cytokines associated with T helper 1 and T helper 2 cells is not fully elucidated. This study aimed to evaluate the role of T helper 1 and T helper 2 cytokines in both remission and activity phases among atopic versus nonatopic children with SSNS. Fifty-two children with SSNS (21 with atopic disorders and 31 nonatopics) and 60 healthy children were enrolled in the study. The healthy controls were comparable with the patients in terms of age and sex distribution. Serum levels of immunoglobulin E (IgE), interleukin (IL)-2, tumor necrosis factor (TNF)-α, IL-4, and IL-13 were measured in activity and remission phases of the disease and in controls. Serum levels of IgE, TNF-α, IL-4, and IL-13 were significantly increased in the children with SSNS during the active compared to remission phase and the controls. T helper 2 markers (IgE, IL-4, and IL-13) were also higher in the atopic patients with SSNS than those without atopy. No significant difference was observed in IL-2 levels between the SSNS children in activity and remission phases and the controls, or between atopic and nonatopic children with SSNS in activity and remission phases. Our findings suggested that type 2 immune response prevailed during the active stage in children with SSNS, atopic or not, with persistent elevation of IgE during remission. T helper 2 imbalance was markedly exaggerated in atopic children.

Cisplatin is a widely used chemotherapeutic agent with a major side effect of nephrotoxicity. Delayed increase in serum creatinine after cisplatin injection makes serum creatinine not to be an ideal marker for early detection of cisplatin nephrotoxicity. Recently several new biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) have been proposed for early detection of acute kidney injury (AKI). This study assessed kinetic of urine NGAL-creatinine ratio in patients who received cisplatin-containing chemotherapy. Patients with a glomerular filtration rates greater than 45 mL/min who received cisplatin-containing chemotherapy were included. Urine creatinine and NGAL concentrations were measured before cisplatin infusion and 6, 24, 48, and 72 hours after cisplatin administration. To minimize hydration effects, urine NGAL levels were adjusted according to urine creatinine. Twenty-four patients were assessed. According to the Acute Kidney Injury Network criteria, 2 patients (8%) experienced cisplatin-associated AKI. The median increases in urine NGAL-creatinine ratio were 335% (interquartile range, 320% to 350%) in the patients with AKI and 100% (interquartile range, 73% to 190%) in those without AKI (P =. 02) during the first 24 hours after cisplatin administration. A urine NGAL-creatinine ratio greater than 26.9 ng/mg 24 hours after cisplatin infusion had a sensitivity of 86% and a specificity of 50% to detect cisplatin-associated nephrotoxicity. Urine NGAL-creatinine ratio significantly increased in patients with cisplatin-associated AKI. Urine NGAL-creatinine ratio within the first 24 hours after cisplatin infusion may better predict cisplatin-associated nephrotoxicity than serum creatinine level.

Proteinuria is the most reliable marker of diabetic nephropathy and an index of atherosclerosis and cardiovascular mortality in diabetic patients. In addition, common carotid artery intima-media thickness (CIMT) is a sensitive marker of early atherosclerosis and cardiovascular risk. The aim of this study was to evaluate the association between proteinuria and CIMT in type 2 diabetic patients. In a cross-sectional study, 154 patients with type 2 diabetes mellitus were enrolled. The CIMT was measured for all of the patients by one researcher. The 24-hour urine protein was measured using trichloroacetic acid method. A total of 154 type 2 diabetic patients were enrolled with a mean diabetes mellitus duration of 8.91 ± 6.99 years (95 women and 55 men). The mean urinary protein in the patients was 294.70 ± 525.85 mg/24 h. The mean CIMT in all of the patients was 0.84 ± 0.19 mm, and it was greater in the men than in the women (P =. 03). The CIMT significantly correlated with patients'' age (P <. 001), systolic blood pressure (P <. 001), and urinary protein excretion (P =. 001). There was a marginal positive correlation between diabetes mellitus duration and the CIMT (P =. 049). This study showed a significant association between CIMT, as a sensitive marker of macrovascular complication of diabetes mellitus, and proteinuria as an important index of microvascular complication of the disease.

Uremic pruritus is a common complication in patients with chronic kidney disease. While its cause is not known for certain, different treatments are currently applied. This study aimed to compare the effects of Avena sativa, diluted vinegar, and hydroxyzine on the reduction of uremic pruritus. In this crossover randomized clinical trial, 23 hemodialysis patients with uremic pruritus were randomly divided into 3 groups. The first group was treated with Avena sativa lotion, twice a day, for as long as 2 weeks; the second group received diluted vinegar; and the third group took hydroxyzine tablets for the same time span. After 3-day-long washout periods, the therapeutic methods were crossed over. The data were collected by a pruritus scale and a visual analogue scale, which were completed before and after the interventions. Avena sativa lotion significantly decreased the mean scores of pruritus intensity, consequences, and the verbal descriptor, although it did not have a significant effect on the frequency of pruritus and the pruritic surface. Vinegar and hydroxyzine significantly decreased all of the scores. Avena sativa, vinegar, and hydroxyzine were effective in decreasing pruritus. Diluted vinegar and Avena sativa can be used as a complement to hydroxyzine, which is itself a common pharmaceutical therapy.

Intradialytic hypotension (IDH) has been reported in 15% to 50% of hemodialysis patients and increases patients morbidity and mortality. Some small noncontrolled studies evaluated the effect of sertraline on IDH with conflicting results. This study is a randomized crossover controlled trial on the effectiveness of sertraline to reduce IDH. Patients on hemodialysis who suffered IDH in at least 50% of their dialysis sessions were enrolled. Each patient received either sertraline or placebo for 4 weeks and after a 4-week washout period, was switched to the other arm of the trial. All patients started sertraline at a daily dose of 50 mg that increased to 100 mg after 1 week. Twelve patients completed all phases of the study. Sertraline therapy increased nadir intradialysis diastolic and systolic blood pressure by 3.8 mm Hg and 4.9 mm Hg at the end of the intervention, respectively. Sertraline therapy also significantly increased postdialysis diastolic and systolic blood pressure by 6.0 mm Hg and 8.7 mm Hg. Sertraline therapy significantly reduced the risk of hypotension episodes by 43%. The improvement of intradialysis and postdialysis diastolic and systolic blood pressure were only significant in nondiabetic patients. Sertraline therapy significantly increases intradialysis and postdialysis blood pressure. These effects of sertraline can result in significant decrease in hypotension episodes during dialysis treatment and the number of interventions required to manage IDH. However, not all patients may benefit from sertraline depending on comorbidities such as diabetes mellitus.

Elevated level of bile can cause bile cast nephropathy, which can be seen in patients with severe cholestatic liver disease. Stanozolol is a C17α-alkylation steroid derived from dihydrotestosterone and its major adverse effect is cholestatic jaundice. We report 2 bodybuilders who received stanozolol for 6 weeks and developed icterus. Serum total bilirubin was around 50 mg/dL. Liver biopsy showed intrahepatic cholestasis. In spite of fluid and albumin therapy, serum creatinine increased and the patients experienced oliguria. Urine sediment showed granular cast and normal erythrocyte count. Protein excretion in 24-hour urine was less than 1000 mg in both patients. Hemodialysis was started on and renal biopsy revealed acute tubular epithelial cell damage along with bile pigment (cast) deposition, compatible with bile cast-related nephropathy. Serum bilirubin decreased gradually and urine output increased. Serum creatinine was around 1.5 mg/dL in both of the patients 2 months after discharge.