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Interstitial nephritis [keywords]
- Estimation of kidney injury molecule-1 (Kim-1) in patients with lupus nephritis. [JOURNAL ARTICLE]
- Lupus 2014 Mar 5.
ObjectiveBiomarkers of disease activity in lupus nephritis (LN) are needed. Ideally, such biomarkers would be capable of detecting early sub-clinical disease and could be used to gauge response to therapy, thus obviating the need for serial renal biopsies. Much of the focus in the search for LN biomarkers has been on the measurement of urinary chemokines and cytokines in LN patients. However, these have yet to be widely implemented in clinical practice. Kidney injury molecule-1 (Kim-1) is expressed in damaged tubules, but whether urinary (u) and tubular (t)-Kim-1 could serve as a biomarker of active LN is unknown. To investigate the disease activity and histological findings in LN, we evaluated u-Kim-1 levels and t-Kim-1 cells in patients with systemic lupus erythematosus (SLE).MethodWe measured u-Kim-1 levels and stained t-Kim-1 expression in 57 patients with LN using an ELISA and immunohistochemistry staining. Patients were classified into two groups (active LN, n = 37; inactive LN, n = 20) based on the presence of active renal disease according to the renal SLE disease activity index. correlations of clinical, laboratory data, and histological findings with urinary and t-Kim-1 expression were assessed.ResultThe u-Kim-1 levels were significantly correlated with the expression of t-Kim-1 (R = 0.64; P = 0.004) in the SLE patients. The active LN patients exhibited elevated u-Kim-1 levels compared to the inactive LN patients. The number of t-Kim-1 cells was also correlated with histological findings (both glomerular and interstitial inflammation). The u-Kim-1 levels were also correlated with proteinuria and tubular damage in the active LN group. The number of t-Kim-1 cells at baseline was significantly correlated with the estimated glomerular filtration rate (R = 0.72; P = 0.005) and serum creatinine (R = 0.53; P = 0.005) after 6-8 months of treatment.ConclusionThese data suggest the potential use of the u-Kim-1 levels to screen for active LN and for the estimation of t-Kim-1 expression in renal biopsies to predict renal damage, ongoing glomerular nephritis and tubulointerstitial inflammation, and tubular atrophy.
- Origin of porcine circovirus type 2 (PCV2) from swine affected by PCV2-associated diseases in Croatia. [JOURNAL ARTICLE]
- Vet Rec 2014 Mar 3.
Porcine circovirus type 2 (PCV2) causes some of the most significant economic losses in pig production. Several multisystemic syndromes have been attributed to PCV2 infection, which are known as PCV2-associated diseases (PCVDs). This study investigated the origin and evolution of PCV2 sequences in domestic pigs and wild boars affected by PCVDs in Croatia. Viral sequences were recovered from three wild boars diagnosed with PCV2-systemic disease (PCV2-SD), 63 fetuses positive for PCV2 DNA as determined by PCR, 14 domestic pigs affected with PCV2-SD (displaying severe interstitial nephritis) and five domestic pigs with proliferative and necrotising pneumonia. Seventeen complete PCV2 genomes were recovered. Phylogenetic and evolutionary analyses based on median-joining phylogenetic networks, amino acid alignments and principal coordinate analysis were performed using complete genomes, as well as complete and partial ORF sequences for ORF1 and ORF2. Two of the 17 PCV2 sequences belonged to PCV2a, 14 to PCV2b and one was unclustered. PCV2b was the predominant genotype in Croatia and has been linked to international trade as a route of introduction. Correlation between particular viral strains with PCVDs is lacking.
- Phenazopyridine associated acute interstitial nephritis and review of literature. [JOURNAL ARTICLE]
- Ren Fail 2014 Feb 27.
Abstract Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridine-induced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage.
- Exaggerated renal fibrosis in P2X4 receptor-deficient mice following unilateral ureteric obstruction. [JOURNAL ARTICLE]
- Nephrol Dial Transplant 2014 Feb 25.
The ATP-sensitive P2X7 receptor (P2X7R) has been shown to contribute to renal injury in nephrotoxic nephritis, a rodent model of acute glomerulonephritis, and in unilateral ureteric obstruction (UUO), a rodent model of chronic interstitial inflammation and fibrosis. Renal tubular cells, endothelial cells and macrophages also express the closely related P2X4 receptor (P2X4R), which is chromosomally co-located with P2X7R and has 40% homology; it is also pro-inflammatory and has been shown to interact with P2X7R to modulate its pro-apoptotic and pro-inflammatory effects. Therefore, we chose to explore the function of P2X4R in the UUO model of renal injury using knockout mice. We hypothesized that UUO-induced tubulointerstitial damage and fibrosis would also be attenuated in P2X4R(-/-) mice.P2X4R(-/-) and wild-type (WT) mice were subjected to either UUO or sham operation. Kidney samples taken on Days 7 and 14 were evaluated for renal inflammation and fibrosis, and expression of pro-fibrotic factors.To our surprise, the obstructed kidney in P2X4R(-/-) mice showed more severe renal injury, more collagen deposition (picrosirius red staining, increase of 53%; P < 0.05) and more type I collagen staining (increase of 107%; P < 0.01), as well as increased mRNA for TGF-β (increase of 102%, P < 0.0005) and CTGF (increase of 157%; P < 0.05) by Day 14, compared with the UUO WT mice.These findings showed that lack of P2X4R expression leads to increased renal fibrosis, and increased expression of TGF-β and CTGF in the UUO model.
- Cytomegalovirus glomerulopathy and cytomegalovirus interstitial nephritis on sequential transplant kidney biopsies. [Journal Article]
- Am J Kidney Dis 2014 Mar; 63(3):536-9.
Cytomegalovirus (CMV) nephropathy may be seen in kidney transplant biopsy specimens. We report a CMV-negative patient who received a kidney transplant from a CMV-positive donor and subsequently developed CMV glomerulopathy and CMV-associated interstitial nephritis, as observed in 2 sequential kidney biopsies. The first biopsy specimen showed CMV-positive endothelial cells in glomerular capillaries and CMV-infected monocytes in glomerular capillary lumens. The second biopsy specimen showed CMV-positive cells in the interstitium with associated lymphoplasmacytic infiltrate and tubular injury, but no evidence of direct CMV infection in tubular epithelial cells. Moreover, the second biopsy specimen showed persistent monocytes with cytoplasmic viral particles within glomerular capillary loops by electron microscopy. Our case shows that CMV glomerulopathy can be caused by direct CMV infection of glomerular capillary endothelial cells. CMV-positive circulating monocytes may play an important role in the different histopathologic manifestations of CMV nephropathy in kidney transplant grafts.
- [Granulomatous interstitial nephritis in a patient with Behçet's disease treated with infliximab]. [English Abstract, Journal Article]
- Nihon Jinzo Gakkai Shi 2013; 55(8):1412-7.
The patient is a 41-year-old man diagnosed with uveitis in 2004. Although the patient was positive for HLA-B51, the primary disease could not be identified, and oral administration of prednisolone (PSL) was initiated. A subsequent gradual decrease in the PSL dose was accompanied by the development of recurrent spasmodic chorioretinopathy and hypopyon. In November 2007, the patient was diagnosed with Behçet's disease based on the findings of erythema nodosum, acneiform eruption, and oral aphtha. In order to control the ocular symptoms, infliximab was administered. However, the patient's renal function began to deteriorate in November 2011, and he was transferred to our department after 6 months. At that time, his creatinine level was 8.56 mg/dL. Renal biopsy examination revealed granulomatous interstitial nephritis. Moreover, only infliximab yielded a positive result in a drug-induced lymphocyte stimulation test (DLST). Following initiation of PSL administration at 60 mg/day, his renal function improved. His creatinine level remained constant at approximately 3 mg/dL. In the present case, Behçet's disease, sarcoidosis, and infection were excluded as the underlying disease causing granulomatous interstitial nephritis. Moreover, infliximab is reportedly involved in the development of granulomas. Recent reports have stated that administration of TNF-alpha inhibitors occasionally results in the development of granulomas in the lungs and skin, and sometimes, in the kidneys as well. When renal dysfunction occurs in patients receiving TNF-alpha inhibitors, we believe that it is essential to include adverse events associated with TNF-alpha inhibitors in the differential diagnoses.
- The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis. [JOURNAL ARTICLE]
- Lupus 2014 Feb 17.
Objective: The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Methods: Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. Results: The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, p<0.001; 44.1 ± 46.8 ng/ml vs. 22.8 ± 3.0 ng/ml, p = 0.035, respectively). There was no significant difference of the serum connective tissue growth factor levels between non-renal systemic lupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, p<0.001) and acute renal failure (85.5 ± 75.0 ng/ml vs. 31.2 ± 21.8 ng/ml, p = 0.002). Serum connective tissue growth factor levels in class IV were significantly higher than that in class II, III and V (57.6 ± 57.5 ng/ml vs. 18.7 ± 6.4 ng/ml, p = 0.019; 57.6 ± 57.5 ng/ml vs. 25.2 ± 14.9 ng/ml, p = 0.006; 57.6 ± 57.5 ng/ml vs. 30.5 ± 21.3 ng/ml, p = 0.017, respectively). Serum connective tissue growth factor levels were significantly higher in those with both active/chronic lesions than those in those with active lesions only in either class IV (84.9 ± 69.6 ng/ml vs. 40.0 ± 40.2 ng/ml, p = 0.001) or in combination of class III and IV lupus nephritis (63.3 ± 63.4 ng/ml vs. 38.3 ± 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, p<0.001) and positively associated with interstitial inflammation (r = 0.309, p = 0.002) and interstitial fibrosis (r = 0.287, p = 0.004). Serum connective tissue growth factor level was a risk factor for doubling of serum creatinine in lupus nephritis (p<0.001, hazard ratio = 1.015, 95% confidence intervals 1.008-1.022) in univariate analysis. Conclusions: Serum connective tissue growth factor levels were significantly higher in lupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis.
- Granulomatous nephritis consistent with malakoplakia in a cynomolgus monkey. [Journal Article]
- J Toxicol Pathol 2013 Dec; 26(4):419-22.
Malakoplakia is a rare form of chronic granulomatous inflammation in mammals, and usually affects the urinary tract in humans. In this report, we present a case of granulomatous nephritis consistent with malakoplakia in a 4-year-old male cynomolgus monkey. Gross examination showed that the kidney was markedly enlarged and adhered to the surrounding organs. Histology showed that there was diffuse interstitial infiltration of histiocytes with abundant foamy eosinophilic cytoplasm resembling von Hansemann cells, PAS-positive granular cytoplasm and occasional PAS- and iron-positive intracellular small inclusion bodies. Electron microscopy showed that these histiocytes contained abundant lysosomes and phagolysosomes but no obvious Michaelis-Gutmann bodies. Based on these findings, a diagnosis of granulomatous nephritis consistent with early malakoplakia was made. This is the first report in a monkey of a renal lesion consistent with malakoplakia.
- Paraquat Exposure Up-regulates Cyclooxygenase-2 in the Lungs, Liver and Kidneys in Rats. [Journal Article]
- Iran J Pharm Res 2013; 12(4):887-96.
Paraquat is a commonly used herbicide in many countries which can lead to systematic poisoning on exposure, In this study, paraquat (PQ)-induced changes in the expression of Cyclooxygenase-2 (COX-2) along with biochemical and histopathological changes in the lungs, liver and kidneys were studied. Twenty four male Wistar rats (180-200 g) were exposed either against saline as control group or various doses of PQ (3.5, 7 and 10 mg/kg, SC) as test groups for 7 consecutive days. The animals in test groups demonstrated a significant increase of malondialdehyde and NO contents, while a remarkable decrease of total thiol molecules was recorded. Histopathological studies revealed a severe alveolar edema and hemorrhages in the lungs, congestion and glycogen degeneration in the liver and multifocal interstitial nephritis along with proximal tubular degeneration in the kidneys. PQ up-regulated the COX-2 expression at mRNA level significantly in the examined organs. This data suggest that the PQ-induced oxidative disturbances and pathological damages can be attributed to the upregulation of COX-2 in examined organs.
- A mouse Col4a4 mutation causing Alport glomerulosclerosis with abnormal collagen α3α4α5(IV) trimers. [JOURNAL ARTICLE]
- Kidney Int 2014 Feb 12.
A spontaneous mutation termed bilateral wasting kidneys (bwk) was identified in a colony of NONcNZO recombinant inbred mice. These mice exhibit a rapid increase of urinary albumin at an early age associated with glomerulosclerosis, interstitial nephritis, and tubular atrophy. The mutation was mapped to a location on chromosome 1 containing the Col4a3 and Col4a4 genes, for which mutations in the human orthologs cause the hereditary nephritis Alport syndrome. DNA sequencing identified a G-to-A mutation in the conserved GT splice donor of Col4a4 intron 30, resulting in skipping of exon 30 but maintaining the mRNA reading frame. Protein analyses showed that mutant collagen α3α4α5(IV) trimers were secreted and incorporated into the glomerular basement membrane (GBM), but levels were low, and GBM lesions typical of Alport syndrome were observed. Moving the mutation into the more renal damage-prone DBA/2J and 129S1/SvImJ backgrounds revealed differences in albuminuria and its rate of increase, suggesting an interaction between the Col4a4 mutation and modifier genes. This novel mouse model of Alport syndrome is the only one shown to accumulate abnormal collagen α3α4α5(IV) in the GBM, as also found in a subset of Alport patients. These mice will be valuable for testing potential therapies, for understanding abnormal collagen IV structure and assembly, and for gaining better insights into the mechanisms leading to Alport syndrome, and to the variability in the age of onset and associated phenotypes.Kidney International advance online publication, 12 February 2014; doi:10.1038/ki.2013.493.