Iranian Journal of Kidney Diseases
Volume:7 Issue: 5, Sep 2013

Hemolytic-uremic syndrome (HUS) is a rare life-threatening disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and impaired renal function. A thrombotic microangiopathy underlies the clinical features of HUS. In the majority of cases, HUS follows an infection with toxin-producing bacteria such as verotoxin-producing Escherichia coli. In some cases, HUS is not preceded by a clinically apparent infection, and therefore, is named atypical HUS. The prognosis of atypical HUS is poor. While mortality approaches 25% during the acute phase, end-stage renal disease develops in nearly half of patients within a year. Evidence is accumulating that complement activation through the alternative pathway is at the heart of the pathophysiology leading to atypical HUS. Genetic abnormalities involving complement regulatory proteins and complement components form the molecular basis for complement activation. Since microvascular thrombosis is a quintessential feature of atypical HUS, complements and the coagulation system must work in tandem to give rise to the pathologic alterations observed in this condition. Here, a brief discussion of clinical and morphologic features of atypical HUS is followed by a concise presentation of the complement and coagulation systems. The interplay between complements and the coagulation system is graphically highlighted. Last but not least, conventional and emerging therapies for atypical HUS are outlined.

Diabetic nephropathy is the leading cause of chronic kidney disease and end-stage renal disease. Oxidative stress has been recognized as a major contributor to its pathogenesis. Defensive mechanisms have also widely been studied. One of them, the NF-E2-Related Factor 2, is reviewed in this article.

We present a rare complication of transplant renal artery stenting in a patient who developed subcapsular hematoma and presented as acute page kidney. We discuss possible mechanisms and successful novel management using radiological-assisted decompression. We propose considering this alternative option before proceeding with surgical exploration and renal capsulotomy.

Mutations in podocin (NPHS2) gene have the key role in the pathogenesis of steroid-resistant nephrotic syndrome (SRNS) in children, but data is scarce regarding their prevalence and natural course among different all ethnic groups. This study was aimed to demonstrate the spectrum of NPHS2 mutations in children with SRNS and to compare the clinical course of disease in patients with and without mutation. All 8 exons of NPHS2 were sequenced in 99 children, including 49 with SRNS and 50 with steroid-sensitive nephrotic syndrome (control group) by DNA sequencing. The prevalence rates of NPHS2 gene mutation among children with SRNS and SSNS were 31% and 4%, respectively. The prevalence rates of mutation among familial and sporadic forms were 57% and 26%, respectively. Thirty-three percent of the children experienced recurrence of primary disease after kidney transplantation, none of whom had a mutation. The clinical response to treatment was poorer in children with mutation in comparison with patients without mutation (12% versus 32%, respectively; odds ratio, 3.29, 95% confidence interval, 0.40 to 25.64). Patients with and without mutation could not be differentiated by demographic and histological features, glomerular filtration rate at onset, hypertension, progression to end-stage renal disease, and proteinuria. Mutations of NPHS2 gene are frequent among Iranian children with SRNS. Regarding similar clinical features in patients with and without mutation and poor response to pharmacotherapy in patients with mutation, a molecular approach might be necessary for different treatment plans and prediction of prognosis.

There is still controversy regarding the possible role of chronic functional constipation in disorders of the urinary tract, specifically urinary tract infection (UTI) and enuresis. The aim of this study was to investigate the frequency of (UTI) and enuresis in children with chronic functional constipation. We included 120 children (60.8% girls) with chronic functional constipation based on the Rome III criteria. Detailed history of UTI and enuresis or symptoms pointing to these diagnoses was obtained. Urinalysis, urine culture, and abdominal ultrasonography were performed for all of the participants. The mean age of the patients was 7.4 ± 3.2 years. Seventy-five percent of the patients had constipation for more than 1 year. The most common urinary symptoms were dysuria (16.7%), urinary frequency (12.5%), and dribbling (4.2%). The frequencies of nocturnal and daytime enuresis were 22.5% and 3.3%, respectively. Pyuria was seen in 10 girls (8.3%). Overall, 7 patients (5.8 %) had a positive urine culture, of whom all were girls and 6 had pyuria. Urinary tract ultrasonography was normal in these patients. Urinary symptoms, especially nocturnal enuresis, were found in a significant number of children who had chronic functional constipation, but UTI was not so common in the present study. Therefore, we suggest that nocturnal enuresis be considered in children with chronic functional constipation, but screening for UTI is not recommended in these patients.

Reperfusion injury leads to damage to the hemodynamic and functional parameters of the kidney. This study investigated the effects of oral administration of the aqueous extract of rosemary on improvement of changes induced by ischemia-reperfusion in rats. Fourty male Sprague-Dawley rats were divided into 4 groups. One group was the control, rates in another group underwent sham operation, and 2 groups were exposed to reperfusion injury. Rats in one of the reperfusion groups was treated with 8% oral aqueous extract of rosemary (10 mL/kg/d) for 1 week (rosemary group), and the other received normal saline for the same period of time (reperfusion group). Reperfusion injury was induced by bilateral occlusion of the renal artery and vein for 30 minutes and reperfusion for 24 hours. Examination of oxidative stress was done, including measurement of malondialdehyde and ferric reducing antioxidant power in urine and blood samples. Histological studies were performed on excised kidneys. The comparison between the rosemary and reperfusion groups indicated significant reductions in the levels of plasma creatinine, blood urea nitrogen, and absolute urinary excretion of sodium in the rosemary group. Similarly, the rosemary group presented a significant decrease in malondialdehyde and a significant increase in ferric-reducing antioxidant power. Histopathological examinations showed significant reductions in vascular congestion and cells exfoliation in the rosemary group, in comparison with the reperfusion group. Oral administration of the aqueous extract of rosemary prior to ischemia-reperfusion is effective in reducing functional and histopathological complications associated with acute kidney failure.

Nephrotoxicity is a serious side effect of gentamicin and is believed to be related to reactive oxygen species in the kidney. This study was aimed to find out whether garlic preparation (Allium sativum L) has ameliorative effects on gentamicin nephrotoxicity. Fifty male Wistar rats were divided into 5 groups of 10 as follows: group 1, sham group (control); group 2 (positive control group), gentamicin for 10 days; group 3, garlic and gentamicin for 10 days; group 4, gentamicin for 10 days followed by garlic for 10 days; and group 5, gentamicin for 10 days followed by saline solution for 10 days. Gentamicin, 10 mg/kg, and garlic extract, 20 mg/kg, were administered intraperitoneally. Serum creatinine and concentrations were measured and the kidneys were processed for histopathological examinations. All specimens were examined for morphologic parameters involving tubular cells. Serum creatinine and BUN levels were significantly high in the gentamicin group (group 2) after the experiment. However, the levels of these parameters in group 3 (co-treatment with gentamicin and garlic) were significantly lower than those in group 2 (P <. 05). These parameters were also lower in group 4 (consecutive treatment with gentamicin and garlic), when compared with group 5 (gentamicin and saline). The pathology damage score was high for the gentamicin group. Postadministration of garlic after gentamicin treatment (group 4) or co-administration of garlic and gentamicin (group 3) significantly attenuated the damage score. Garlic has regenerative potential after tubular injury induced by gentamicin in animal models.

The protective role of recombinant human erythropoietin (RHE) against cisplatin-induced nephrotoxicity has been reported, but the role of sex differences is not clearly known. The aim of this study was to determine the sex-based difference in the protective effect of RHE against cisplatin-induced nephrotoxicity. Thirty-three Wistar rats were divided into 6 groups. According to protocol l, male and female rats were treated with RHE (100 IU/kg/d) for 3 days and then received a single dose of cisplatin (7 mg/kg). According to protocol 2, the rats received the same single dose of cisplatin and then were treated with RHE for 7 days. Two other groups of male and female rats received a similar regimen of protocol 2 except for saline instead of RHE. All the animals were sacrificed 1 week after cisplatin administration. All of the experimental animals experienced weight loss. The percentage change of weight in male rats with protocol 1 was significantly less than that in male rats in protocol 2 and control groups. However, in female groups, the percentage of change in weights was slightly higher with protocol 2 than with protocol 1 and control treatment. Administration of RHE significantly decreased changes in serum creatinine, BUN, and malondialdehyde levels in male rats, but not in females. No significant difference was observed in serum nitrite level, kidney weight, and kidney damage score between the groups.This study suggested that erythropoietin may lead to different responses against cisplatin-induced nephrotoxicity in male and female rats.

Chandraprabha Vati (CV) is an Indian polyherbal Siddha drug, traditionally used as an anti-inflammatory agent for arthritis and urinary ailments. This study explores its effect on mice with urinary tract infection. The in-organic constituents of CV were determined by atomic absorption spectroscopy and phytochemical analysis was carried out. The supplementing dose of CV to infected experimental mice was determined by in vitro antimicrobial assay. Transurethrally infected animals were supplemented with CV extract for 20 days after confirmation of UTI. The animals were euthanized as per the guidelines and the tissues were harvested from the control and infected mice for histopathological examination the antimicrobial peptide Tamm-Horsfall protein (THP) and inflammatory markers (tumor necrosis factor-α and nuclear factor kappa-light-chain-enhancer of activated B cells) to ascertain the modulatory effects of CV. Indicators for oxidative stress and protein levels were also quantified to validate the efficacy of CV. Terpenoids and flavanoids were majorly found to constitute CV along with zinc and iron as in-organic content. Histological and immunohistochemical studies confirmed the pronounced infection in the kidney of the uropathogenic Escherichia coli-infected animals. Supplementation of CV significantly restored the increased levels of the antimicrobial proteins, THP, and inflammatory markers. This study explored the efficacy of the aqueous extract of CV as an alternative medication for the synthetic analogues administered for UTI. This study also provides information on the possible role of THP as an antimicrobial protein in the kidney in preventing infection due to uropathogenic E coli.

Depending on the response to standard steroid therapy، nephrotic syndrome it is classified to steroid-sensitive and steroid-resistant nephrotic syndrome (SRNS). Mutations in several genes including NPHS2 have been implicated in SRNS. Gene R229Q polymorphism (p. R229Q) of NPHS2 is associated with adolescent- or adult-onset SRNS in European and South American populations. We investigated this polymorphism among a group of Iranian-Azeri patients with primary SRNS. All participants had the primary late-onset form of focalsegmental glomerulosclerosis (FSGS) and their clinical feature was steroid unresponsiveness. They were compared with a group of age- and sex-matched individuals without any renal disease for NPHS2 gene as controls. The R229Q polymorphism (p. R229Q) was investigated in the case and control groups. A total of 25 patients (mean age، 26. 6 ± 8. 0 years) with primary FSGS and 35 controls (mean age، 26. 0 ± 8. 7 years) were studied. Serum creatinine of patients and their 24-hour protein excretion at the time of study were 2. 4 ± 1. 94 mg/dL and 2830 ± 981 mg/dL، respectively. Molecular study showed no p. R229Q polymorphism، neither in patients nor in controls. In this preliminary study، we showed that NPHS2 gene p. R229Q polymorphism does not present in Iranian-Azeri population with SRNS. Larger studies are needed to confirm our results and other mutated genes should also be considered in these patients.

Bacterial infections are common in patients with nephrotic syndrome, including peritonitis, sepsis, meningitis, urinary tract infection, and cellulitis. An 8-year-old boy presented with colicky abdominal pain, vomiting, swollen and painful erythematous lesions around the umbilicus and in anterior surface of left thigh (cellulitis), mild generalized edema, and ascites. The microorganism isolated from peritoneal fluid and blood cultures was Pneumococcus. Association of pneumococcal sepsis, peritonitis, and cellulitis has been rarely reported in nephrotic syndrome.

Overall success rate of pregnancies in kidney transplant recipients is higher than 90% if pregnancy goes beyond the 1st trimester. Risks to mother include hypertension، preeclampsia، infections، and worsening proteinuria، and those to the fetus are prematurity، intrauterine growth retardation، and low birth weight. Hepatitis B infection is associated with progressive liver disease and diminished survival in kidney transplant recipients. A 32-year-old woman had undergone living unrelated donor kidney transplant. Two years after transplantation، she presented with live gestation of 6 weeks. She was also found positive for hepatitis B surface antigen and extracellular antigen. Liver enzymes were normal and ultrasonography findings were normal. Cyclosporine dose was reduced and lamivudine was started. She was monitored closely until 33 weeks، when she gave birth to a healthy female baby through spontaneous vaginal delivery. The newborn received vaccination and immunoglobulins for hepatitis B virus. Mother''s kidney allograft function remained stable throughout pregnancy.