Iranian Journal of Kidney Diseases
Volume:8 Issue: 5, Sep 2014

Diabetic nephropathy is a major cause of end-stage renal disease throughout the world. Elevated oxidative stress in diabetic patients results from overproduction of reactive oxygen species and decreased efficiency of antioxidant defenses. Moreover, diabetes-associated metabolic disorders impair activities of enzymes of the mitochondrial respiratory chain complex. Therefore, oxidative stress is closely related to mitochondrial dysfunction. This paper reviews studies of mitochondrial dysfunction in diabetic nephropathy.

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common form of primary glomerulopathy worldwide. Various investigations have addressed the clinical and morphological risk factors related to the risk of progression. Recently, much attention has been made toward the prognostic implication of serum uric acid in patients with IgAN. It has been observed that treatment of hyperuricemia with allopurinol in chronic kidney failure has resulted in a fall in blood pressure and inhibition of the progression of kidney injury. Recent studies have documented that hyperuricemia is an independent risk factor for IgAN, and appropriate treatment by allopurinol is a reasonable modality in these patient. We believe that allopurinol should routinely be included to the treatment of IgAN patients; however, this hypothesis requires further investigation. Clinical studies are suggested to better understand kidney protective properties of allopurinol in IgAN.

Dysregulation of CD4+ T cell subsets participates in the pathogenesis of immunoglobulin A nephropathy (IgAN). Vitamin D has immunomodulatory functions. This study aims to investigate the regulatory effect of vitamin D3 on T helper- regulatory T (Th17-Treg) cells balance in rats with IgAN. Sprague-Dawley rats were randomly assigned to a normal group (n = 6), an IgAN model group (n = 5), a prednisone treatment IgAN group (n = 6), a 1,25-dihydroxyvitamin D3 IgAN group (n = 6), and prednisone plus 1,25-dihydroxyvitamin D3 treatment group (n = 6). At week 12, the 24-hour urine protein excretion and erythrocyte count and renal pathological changes were determined, and serum interleukin-17 and Treg cell levels were measured in blood. The urine protein content and the number of erythrocytes were lower in the vitamin D group than in the model group (P <. 01), but higher than in the prednisone groups (P <0.01). The pathological impairments in the glomerular mesangium, renal tubule, and renal interstitium decreased in response to treatment with prednisone with and without 1,25-dihydroxyvitamin D3. Serum interleukin-17 level in the vitamin D and prednisone plus vitamin D groups was lower than in the prednisone group (P <. 05). The Treg cells in the vitamin D and prednisone plus vitamin D groups showed higher levels than in the prednisone group (P <. 01). Vitamin D3 can regulate the Th17/Treg balance and reduce the level of protein and blood in the urine of rats with IgAN.

Recent studies have shown that serum microRNAs have specific expression patterns in some diseases, indicating the potential of using microRNAs to aid diagnosis. This study estimated the levels of microRNAs in patients with nephrotic syndrome compared with healthy controls. In this study, real-time quantitative polymerase chain reaction was used to explore whether there were different expression levels of miR-181a, miR-483-5p, and miR-557 in the serum of patients with nephrotic syndrome subtypes and healthy controls. We measured the three microRNAs in 40 patients with nephrotic syndrome and 16 healthy controls. The circulating levels of miR-483-5p and miR-557 were not significantly upregulated or downregulated, whereas miR-181a was significantly upregulated in patients with nephrotic syndrome as compared with healthy controls. We found that circulating miR-181a had a significantly different expression and could be an effective means to aid diagnosis of nephrotic syndrome. This microRNA is an attractive candidate as a biomarker for nephrotic syndrome.

Patients with chronic kidney disease (CKD) face with uremic toxins. Lactulose could reduce serum urea and creatinine levels and have some effects on lipid profile and bone minerals. The aim of this study was to evaluate effect of lactulose on serum levels of biochemical products in patients with CKD. In this prospective study, 40 patients with stages 3 and 4 of CKD (52.5% men; mean age, 57.5 ± 12.5 years) were evaluated. All patients received lactulose, 30 mL, 3 times per day for 2 months. Blood samples from all participants were collected before and at the end of intervention to examine changes in biochemical parameters, including sodium, potassium, hemoglobin, urea, creatinine, uric acid, leukocyte and platelets count, β2-microglobin, and intact parathyroid hormone. Lactulose significantly decreased urea levels from 70.35 ± 28.00 mg/dL to 64.50 ± 23.51 mg/dL (P =. 04), creatinine levels from 4.04 ± 1.78 mg/dL to 3.45 ± 1.39 mg/dL (P <. 001), uric acid levels from 7.31 ± 1.49 mg/dL to 6.71 ± 1.42 mg/dL (P <. 001), and β2-microglobin levels from 3.25 ± 0.44 mg/L to 3.08 ± 0.33 mg/L (P =. 001). The decrease in serum electrolytes, lipid profile, and intact parathyroid hormone levels were not significant. Lactulose administration in CKD patients could decrease levels of various deleterious elements, especially nitrogen products, and its daily use can be recommended in these patients.

Aminoglycosides nephrotoxicity limits their use in clinical practice. Growth hormone-releasing peptide-6 (GHRP6) and epidermal growth factor (EGF) have proven cytoprotective effects in various tissues, including the kidney. This study aimed to determine the cytoprotective effect of EGF and GHRP6 on glomerular, proximal tubular, and interstitial morphology in rats treated with an overdose of kanamycin. Forty-four male Wistar adults rats were submitted to treatment for 20 days with sodium phosphate saline buffer (control group), kanamycin (kanamycin group), kanamycin and EGF (EGF group), kanamycin and GHRP6 (GHRP6 group), kanamycin, EGF, and GHRP6 (EGF-GHRP6 group). The kidneys were studied both during acute kidney injury (n = 19) and recovery phases (n = 25). The percentages of glomerular damage, tubular damage (reversible and irreversible changes), and interstitial damage were quantified in 10 histological fields per kidney using paraffin-embedded sections. The damage in the glomeruli, proximal tubules, and interstitium was less in the groups treated with the cytoprotective treatments than in kanamycin group during acute kidney injury. During the recovery phase, normal structure of several glomeruli and the interstitium was appreciated in the EGF and GHRP6 groups, although tissue repair was not as complete as it in the EGF-GHRP6 group. In the recovery phase, cytoprotective treatments accelerated the recovery of tubular damage and reversible tubular changes prevailed. These results confirm the cytoprotective properties of EGF and GHRP6 alone and in combination and suggest the possibility of using these agents to accelerate kidney tissue repair after aminoglycoside-induced renal damage.

Idiopathic nephrotic syndrome (INS) is a common chronic illness in childhood and is initially treated with corticosteroids. Recent reports indicate that the incidence of steroid resistance and focal segmental glomerulosclerosis is on the rise. However, these reports involved different ethnic populations. The purpose of this study was to compare the characteristics of INS in Iranian children in different periods. A retrospective chart review of children admitted with the diagnosis of new-onset INS was performed. Patients were divided into two groups based on date of presentation periods of 1991 to 2002 and 2005 to 2012. Steroid resistance was defined as persistent proteinuria (2+ and more) within 8 weeks of oral corticosteroid treatment. A total of 238 children included in this study (119 in each group). There was an insignificant decrease in the frequency of steroid resistance, along with an insignificant change in histopathology towards focal segmental glomerulosclerosis. These findings indicate that in contrast to other reports of INS from various ethnic compositions, a tendency to steroid resistance is still arguable in the population of Iranian children.

Low fetuin-A and 1,25-hydroxyvitamin D3 (vitamin D) levels accompanied with high intact parathyroid hormone (PTH) contents are associated with cardiovascular disease in dialysis patients. The aim of present study was to evaluate the relationship between vitamin D receptor (VDR) gene FokI and ApaI polymorphisms with serum levels of fetuin-A, vitamin D, and intact PTH in hemodialysis patients. Serum was obtained from 46 stable chronic hemodialysis patients and 43 healthy controls. Serum levels of intact PTH, fetuin-A, vitamin D, calcium, and phosphorus were measured. Genotyping of the VDR gene was performed using standard methods. Serum fetuin-A and vitamin D levels were significantly lower, whereas serum levels of PTH, calcium, and Phosphorus were higher in the hemodialysis patients than in the healthy controls. The FokI genotypes were more frequent in the hemodialysis patients than the control group (P =. 004). With respect to FokI genotypes, intact PTH level was higher among the hemodialysis patients compared to the controls (P =. 02). In contrast, vitamin D level was lower in the hemodialysis patients with ApaI genotypes compared to the control group (P =. 04). Our study shows that increased serum level of PTH and decreased fetuin-A and vitamin D levels may increase susceptibility of atherosclerosis in patients with hemodialysis through VDR gene FokI and ApaI polymorphisms.

Clinical studies of recent years have shown that hyperuricemia is associated with poor outcomes such as cardiovascular mortality and dialysis inadequacy in patients undergoing hemodialysis. Our study investigated the effect of vitamin C supplementation on serum uric acid levels in hemodialysis patients. This randomized placebo-controlled trial was conducted on 172 hemodialysis patients. They were randomly divided into the intervention group, to receive 250 mg of vitamin C, three times per week, for 8 weeks, and control groups 1 and 2, to receive placebo injection (saline) and no intervention, respectively. Serum levels of uric acid and creatinine were measured at the start of the study and also after 8 weeks. The mean of serum levels of uric acid was 6.02 ± 1.08 mg/dL (reference range, 2.6 mg/dL to 6 mg/dL). Nearly, half of the patients (46.7%) had a serum level of uric acid greater than 6 mg/dL. The median baseline serum levels of uric acid were 6.2 mg/dL, 5.9 mg/dL, and 6 mg/dL in the intervention, control 1, and control 2 groups, respectively (P =. 19). After 2 months, median levels reduced significantly in the vitamin C group to 5.8 mg/dL as compared to 6.4 mg/dL and 6.3 mg/dL in control groups (P =. 02). The mean serum creatinine level had no significant changes during the study. Our results demonstrated the existence of a significant negative relationship between vitamin C and serum uric acid levels. Detailed investigations with larger sample sizes and longer-term use of vitamin C are recommended.

The aim of this study was to assess the effects of pioglitazone on blood glucose control and inflammatory biomarkers in diabetic patients receiving insulin after kidney transplantation. In a randomized placebo-controlled trial, 62 diabetic kidney transplant patients were followed for 4 months after randomly assigned to placebo and pioglitazone (30 mg/d) groups. All of the patients continued their insulin therapy irrespective of the group that they were assigned to, in order to evaluate the effects of addition of pioglitazone on blood glucose and inflammation biomarkers including serum C-reactive protein, high-sensitivity C-reactive protein, and interleukin-18 levels, as well as erythrocyte sedimentation rate. At baseline, there were no significant differences in laboratory studies between the two groups. After 4 months of intervention, along with significant improvement in hemoglobin A1c in the pioglitazone group, daily insulin requirements also decreased and lipid profile improved significantly. In addition, erythrocyte sedimentation rate, C-reactive protein, and high-sensitivity C-reactive protein values were significantly lower in the pioglitazone group (P =. 03, P <. 001, and P =. 01). Interleukin-18 levels were not significantly different at the end of the study between the two groups, but it had a decreasing trend in the pioglitazone group (P =. 002). Pioglitazone complementing insulin in diabetic kidney transplant patients not only improved glycemic control, evidenced by hemoglobin A1c, and reduced daily insulin requirement, but also decreased inflammatory markers which may have an impact on overall cardiovascular events and mortalities beyond glycemic control.

Monoclonal immunoglobulin heavy chain (HC) diseases are rare proliferative disorders of B lymphocytes or plasma cells characterized by the presence of monoclonal α-, µ-, or γ-HC without associated light chains in the blood, urine, or both. We report a 59-year-old woman with a history of Hodgkin disease who developed hypercalcemia, proteinuria, and impaired kidney function. Protein electrophoresis and immunofixation displayed γ-HC without associated light chains in the serum and urine. Pathologic examination demonstrated severe tubulointerstitial nephritis associated with diffuse and strong linear staining of the glomerular and tubular basement membranes as well as Bowman capsules for γ-HC, but not for κ- or λ-light chains. Immunohistochemical examination of the kidney and bone marrow demonstrated numerous CD138+ plasma cells immunoreactive for γ-HC, but not for κ- or λ-light chains. This is the first report of tubulointerstitial nephritis associated with γ-HC deposition and γ-HC restricted plasma cells in the kidney. This report heightens awareness about tubulointerstitial nephritis as a possible manifestation of γ-HC deposition in the kidney.

Isolated pleural involvement is rare in Kaposi sarcoma (KS). We report an unusual case of bloody pleural effusion and ascites associated with KS in a kidney transplant recipient. A 50-year-old man who had received kidney transplantation from a living unrelated donor presented with a massive left-side pleural effusion, ascites, and a skin lesion. The pleural effusion and ascites were bloody. The skin biopsy specimens showed KS infiltration (proliferation of spindle-shaped cells). Immunosuppressive therapy was discontinued. Although chemotherapy with paclitaxel was started, the patient died. To our knowledge, this is the first report of bloody pleural effusion and ascites associated with KS. Kaposi sarcoma can cause concomitant serositis in kidney transplant patients and should be considered as a differential diagnosis.