Iranian Journal of Kidney Diseases
Volume:9 Issue: 1, Jan 2015

Drug-induced acute interstitial nephritis (DAIN) is a common cause of acute kidney injury and often presents as an unexplained rise in serum creatinine level. Kidney biopsy is therefore frequently required to make a definitive diagnosis. The hallmark pathologic features of DAIN are interstitial edema, interstitial inflammation, and tubulitis with a predominance of CD4+ T lymphocytes and mononuclear cells, with variable numbers of eosinophils. This is a result of a type B idiosyncratic non-immunoglobulin-E-mediated immune reaction marked by cell-mediated immune injury to the renal tubulointerstitium. The drug becomes immunogenic via various mechanisms such as haptenization, antigen mimicry, and neo-antigen formation. Renal interstitial dendritic cells, and renal tubular epithelial cells play an important role in further propagating this immunologic injury. Acute DAIN can progress within days to weeks to a chronic form triggered by fibroblast activation and manifested as interstitial fibrosis and tubular atrophy. The mainstay of treatment of DAIN is discontinuation of the offending drug. Incomplete renal recovery is seen in one-third of the patients and depends on the duration of injury prior to diagnosis. Use of steroids for treatment of DAIN makes biological sense, but lack of randomized controlled trials and conflicting data from retrospective studies makes the approach unclear. Positive effects include faster recovery of kidney function, more complete recovery with less chronic kidney disease, and reduced need for chronic dialysis. Therefore, it seems reasonable to employ corticosteroids in patients that do not rapidly improve 3 to 5 days following discontinuation of the offending agent.

Herbs are usually considered as inherently harmless products. Nonetheless, various renal injuries have been reported in association with several herbs. The best-known herb-induced chronic kidney disease is aristolochic acid nephropathy. Aristolochic acid is found in Chinese slim herbs. Balkan endemic nephropathy is nowadays considered as an aristolochic acid nephropathy. Plants of Aristolochiaceae (also known as birthwort, dutchman''s pipe, and somersworth) is named zaravand or chopoghak in Persian and it grows in different mountainous and rural areas of Iran. The fruit and the steam of the Aristolochiacae are named zaravand gerd (nokhod alvand) and zaravand dearaz, respectively, and have different usage in Iranian teadirional such as treatment of headache, back pain, and anxiety. Some patients with end-stage renal disease and bilateral small kidneys have a history of exposure to some herbal remedies. We need to consider the possibility of environmental toxins and even Aristolochia nephrotoxicity as a potential danger in Iran.

Leukocyte count, erythrocyte sediment rate and C-reactive protein are available laboratory markers which may be helpful in prediction of technetium Tc 99m dimercaptosuccinic acid (DMSA) renal scintigraphy results. None of these, however, have enough accuracy for prediction of renal injury and scar. This study was aimed to evaluate the diagnostic accuracy of urinary β2-microglobulin in detection of renal injury in children with acute pyelonephritis. Eighty-nine children between 2 months and 14 years old with the diagnosis of acute pyelonephritis that had no past history of infection in the urinary tract system were enrolled in the study. A standard urine sample according to patients'' age was obtained for urine culture, urinalysis, and urinary β2-microglobulin tests. Blood sample was obtained for leukocyte count, creatinine, blood urea nitrogen, C-reactive protein, erythrocyte sediment rate, and electrolytes tests. All patients underwent DMSA scan. The cutoff point for urinary β2-microglubulin for prediction of positive DMSA scan was 0.8 mg with a sensitivity of 40.9% (95% CI, 26.3% to 56.8%) and a specificity of 84.1% (95% CI, 69.9% to 93.4%), a positive predictive value of 72.0% (95% CI, 50.6% to 87.9%) and an negative predictive value of 58.7% (95% CI, 45.6% to 71.0%). Urinary β2-microglobulin is not enough sensitive and specific to be used as a diagnostic marker for prediction of renal injury. Other common markers such as erythrocyte sediment rate, leukocyte count, and C-reactive protein can be used in combination to predict kidney injury in children with acute pyelonephritis.

Nephrin and podocin proteins, encoded by NPHS1 and NPHS2 genes, are essential for the integrity of the glomerular filter. The present study was aimed to investigate whether NPHS1 rs437168 and NPHS2 rs61747728 genetic variants are involved in the susceptibility to nephrotic syndrome (NS). This case-control study was performed on 108 children with NS and 97 healthy children. Genomic DNA was extracted from whole blood using the salting-out method. Polymorphism of the NPHS1 rs437168 and NPHS2 rs61747728 were detected by amplification refractory mutation system- and tetra primers amplification refractory mutation system-polymerase chain reaction, respectively. The results showed that the NPHS1 rs437168 GA as well as GA+AA genotypes increased the risk of NS in comparison with GG genotype (odds ratio, 4.76, 95% confidence interval, 2.31 to 9.80; P <. 001 and odds ratio, 4.57; 95% confidence interval, 2.31 to 9.04,; P <. 001, respectively). The A allele was associated with increased risk of NS (odds ratio, 3.53; 95% confidence interval, 1.94 to 6.42,; P <. 001) in comparison to the G allele. No association was observed between NPHS2 rs61747728 polymorphism and NS. Our findings indicate that NPHS1 rs437168, but not NPHS2 rs61747728 variant, is associated with NS.

Crescentic glomerulonephritis (CGN) is a fatal disease, rapidly leading to end-stage renal disease. Diagnosis should be accurate and treatment should be started immediately. We investigated the factors associated with the renal prognosis in CGN patients. Forty-one patients with CGN who were followed up at the Nephrology Clinic of Ankara Numune Education and Research Hospital were divided into 2 arms of the dialysis-dependent group after treatment and the group that was followed up without dialysis. Demographic and clinical features along with biopsy findings during time of diagnosis were evaluated for both groups. The mean age was 41.3 ± 17.2 years old and 26 were men. Twenty patients developed end-stage renal disease, requiring long-term dialysis. The dialysis-dependent group had higher serum creatinine levels (8.2 ± 3.6 mg/dL versus 2.6 ± 2.5 mg/dL) and percentages of glomeruli with crescent (83.1 ± 19.1% versus 56.4 ± 11.9%), were more likely to have oligoruia-anuria (90.5% versus 9.5%) and be dialysis-dependent at admission (86.4% versus 13.6%), and had longer elapsed time until the beginning of treatment (18.9 ± 10.4 days versus 10.6 ± 3.0 days) after treatment. At admission, their serum creatinine was greater than 4.2 mg/dL and the rate of crescentic glomeruli was greater than 63%. In patients with CGN, renal prognosis is poor and the time of admission to the hospital, degree of renal insufficiency, presence of oligo-anuria, dialysis requirement, and the percentage of crescentic glomeruli on biopsy are closely related to progression to end-stage renal disease.

This study was aimed to assess the ratio of total cholesterol (TC) to high-density density lipoprotein cholesterol (HDLC) and plasma nitrate levels in patients with ischemic nephropathy receiving statins and niacin extended release (NER). Kidney disease patients with a history of at least 5 year of diabetes mellitus or 10 year of hypertension were screened by renal artery Doppler ultrasonography. Participants were randomly assigned into two groups to receive atorvastatin, 20 mg/d, with and without NER, 500 mg/d, for 16 weeks. Serum levels of lipid profile, creatinine, and nitrate were compared before and after the study. Fifty-four patients received the statin and 51 received statin-NER combination. Both statin and statin-NER groups demonstrated significant decreases in plasma levels of TC and low-density lipoprotein cholesterol. Triglyceride and very low-density lipoprotein cholesterol were significantly lowered only with statin-NER combination. The increase in HDLC level was found in both groups, but significant only with statin-NER combination therapy (P <. 001). Atorvastatin combined with NER reduced TC/HDLC ratio almost double as compared with that of atorvastatin alone (102% and 36.6% reduction, respectively). A similar pattern was observed for nitrate levels (33% and 65%, respectively). These findings indicated that a reduction in TC/HDLC ratio improves endothelial function in renovascular disease and use of NER in combination with atorvastatin may provide better outcomes. This could be helpful in attenuating further vascular damage and associated systemic complications.

Fibroblast growth factor 2 (FGF2) is a potent mitogenic factor of cortical fibroblasts and induces kidney fibrosis. We hypothesized that serum levels of FGF2 has an association with the severity of vesicoureteral reflux (VUR) and renal parenchymal scar. Between 2007 and 2009, a total of 28 children with VUR were enrolled in this study and were compared with 52 healthy children. All children with VUR underwent technetium Tc 99m dimercaptosuccinic acid renal scintigraphy. Fibroblast growth factor 2 was measured in both groups. The mean level of FGF2 was 65.0 ± 19.0 pg/mL in the VUR group and 62.5 ± 15.3 pg/mL in the control group (P >. 05). There was no correlation between serum levels of FGF2 and sex, age, or the grade of VUR. Of the 28 children with VUR, 19 had renal parenchymal scar on dimercaptosuccinic acid renal scintigraphy. The mean serum level of FGF2 was not significantly different in the children with and without renal parenchymal scar. This study showed no correlation between serum FGF2 and renal parenchymal scar or grade of VUR.

Kidney transplantation is associated with rapid loss of bone mineral density (BMD) in the first months after transplantation. The effect of pamidronate on bone loss after transplantation was evaluated in a randomized controlled trial. Forty patients were enrolled in this study (16 in the pamidronate group and 24 in the control group). Pamidrinate was administered as 30-mg intravenous infusion within 2 days after transplantation and 3 months later. All of the patients received calcium and vitamin D supplementation. Laboratory parameters and BMD (lumbar spine and femoral neck) were measured at baseline and 6 months after kidney transplantation. Bone mineral density at the initiation of study had no significant differences between the two groups. In each group, BMD of femoral neck and lumbar spine had no significant differences 6 months after transplantation in comparison to pretransplantation values. There was no significant difference in BMD changes after intervention between two groups. Parathyroid hormone level normalized in both of the pamidronate and control groups 6 months after kidney transplantation. Glomerular filtration rate at the end of study was not significantly different between the two groups. Our study suggests that administration of calcium and vitamin D following transplantation may be beneficial to counterbalance the substantial bone loss occurring within 6 months after transplantation, and addition of pamidronate has no beneficial effect in BMD in this short interval after kidney transplantation.

Delayed graft function (DGF) is a consequence of ischemia-reperfusion injuries in kidney allografts, for which no definite treatment is available. The neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) are introduced as the most promising urine biomarkers to detect DGF. N-acetylcysteine (NAC) and vitamin C, well-known potent antioxidants that scavenge free radicals, may alleviate kidney injury. This study investigated the protective effects of NAC alone and in combination with vitamin C on DGF, by measuring IL-18 and NGAL in living donor kidney transplantations. Patients transplanted between January 2011and February 2013 were randomly divided into 3 groups to receive routine anti-rejection medication only (n = 32), NAC plus routine immunosuppressive regimen (NAC group; n = 33), and NAC and vitamin C plus routine regimen (NAC and vitamin C group; n = 19). Urine samples were taken 4 hours and 24 hours after transplantation. Enzyme-linked immunosorbent assay kits were utilized for measuring urine NGAL and IL-18. There were no significant differences in the DGF prevalence and its duration between the study arms. Although the levels of NGAL and IL-18 decreased in the NAC and NAC and vitamin C groups, these reductions were not significant. Glomerular filtration rate at 30 and 60 days after transplantation were not significantly different between study groups, either. Our results showed that NAC is a safe drug without significant adverse effects in kidney transplant recipients; however, its potential useful effects on urinary biomarkers of DGF were not illustrated in the present study.

Cystinuria, one of the first inborn errors of metabolism, is characterized by hyperexcretion of cystine, arginine, lysine, and ornithine into urine. Cystinuria is genetically classified into types A and B. Mutations in the SLC3A1 gene lead to type A, and type B is caused by mutations in the SLC7A9 gene. We described a 19-year-old woman that had early onset of cystine calculus formation at the age of 3 years. After DNA extraction and polymerase chain reaction, direct sequencing was performed. By these methods, a novel nucleotide substitution c.177G>A in exon 3 of the SLC7A9 gene was found, which had not been reported elsewhere previously. This nucleotide substitution occurs in the extracellular domain of the SLC7A9 gene. In addition, a previously described intron variant c.1136+2/3delT (intron 6 of SLC3A1) in homozygosity status was detected in the patient. To our knowledge, this is the first report of novel nucleotide substitution c.177G>A in exon 3 of the SLC7A9 gene.

Calciphylaxis is a complication of chronic kidney disease characterized by necrotic lesion in the skin. Histological examination reveals microcalcification of medium-sized blood vessels. We report on a 21-month-old girl with end-stage renal disease with severe calcium-phosphate imbalance. Calciphylaxis process started when she received calcium gluconate intravenously the day before the surgery to correct hypocalcemia and continued progressively despite peritoneal dialysis and forced stopping calcium-containing medication. Pamidronate, 0.5 mg/kg/d, was administered for 6 days and then once a week for 5 weeks. After 1 week, the skin lesion started to heal and circulation improved, and after 6 weeks, all skin lesions completely recovered. Pamidronate was effective to stop calciphylaxis in this case with advanced renal insufficiency and severe calcium-phosphate imbalance. Medical or surgical debridement are not suggested and lesions might recover without scar by pamidronate.