Decreased urinary calbindin 1 levels in proteinuric rats and humans with distal nephron segment injuries

Background

Several proteins have been proposed as new urinary biomarkers of kidney injuries, but they are not always capable of identifying the kidney nephron segment that has been injured. Since calbindin 1 protein is exclusively localized in the kidney distal nephron segment, it is presumed that its expression is altered during distal nephron segment injuries, resulting in changes in its urinary excretion.

Methods

Calbindin 1 expression in normal rat kidneys was compared with that in the kidneys of rats that had suffered distal nephron segment injuries (unilateral ureteral obstruction [UUO] or anti-glomerular basement membrane glomerulonephritis [anti-GBM GN]) using immunohistochemical examinations and real-time polymerase chain reaction. The urinary calbindin 1 protein concentration of normal rats was also compared with that of anti-GBM GN rats and of cisplatin nephropathy rats using Western blotting. We also compared the kidney and urinary calbindin 1 protein concentrations of normal human subjects with those of proteinuric patients [immunoglobulin (Ig)A nephropathy; IgAN] with distal nephron segment injuries.

Results

Calbindin 1 mRNA expression in the renal cortices and calbindin 1 protein expression in the kidney distal nephron segments were decreased in the UUO and anti-GBM GN rat kidneys. The urinary calbindin 1 protein levels of the anti-GBM GN rats were also markedly decreased, whereas those of the cisplatin nephropathy rats were slightly decreased. The human IgAN patients displayed decreased renal calbindin 1 protein expression in their dilated distal tubules, and some patients displayed decreased urinary calbindin 1 levels.

Conclusion

Since it has been demonstrated that decreased urinary calbindin 1 levels are indicative of decreased calbindin 1 kidney expression due to distal nephron segment injuries, calbindin 1 might be a useful urinary biomarker for identifying distal nephron segment injuries.     

The complex of immunoglobulin A and uromodulin as a diagnostic marker for immunoglobulin A nephropathy

Background

The only tool to diagnose immunoglobulinn A nephropathy (IgAN) is renal biopsy which requires hospitalization; moreover, renal biopsy has a risk of critical bleeding. Therefore, a non-invasive method for accurate diagnosis of IgAN is desirable and a must-to-have tool for the clinics. For this purpose, we evaluated the diagnostic value of the IgA–uromodulin complex in the urine of patients with IgAN for its feasibility and adequacy.

Method

We determined the IgA–uromodulin complex as a candidate for a diagnostic marker of IgAN by immunoprecipitation, liquid chromatography?mass spectrometry (LC–MS) and Western blot analysis. The enzyme-linked immunosorbent assay (ELISA) for the IgA–uromodulin complex was developed and applied to urine samples obtained from various kidney disease patients.

Result

One hundred and three of 126 urine samples (81.7%) from IgAN patients were positive for the IgA–uromodulin complex, while only 25 out of 94 urine samples (26.6%) in other kidney disease patients were positive. Sensitivity was 81.7%, specificity was 73.4%, and diagnosis efficiency was 78.2%. The complex was negative in eight urine samples obtained from patients with Alport syndrome which is almost impossible to discriminate from IgAN by routine urinalysis.

Conclusion

Detection of the urinary IgA–uromodulin complex by ELISA is a useful non-invasive method to diagnose IgAN.     

Severity of nephrotic IgA nephropathy according to the Oxford classification

Background

IgA nephropathy with nephrotic syndrome (nephrotic IgAN) is a rare form of IgAN. Its prognosis and response to steroid therapy are still controversial because the differential diagnosis between nephrotic IgAN and minimal change nephrotic syndrome with IgA depositions is sometimes confused.

Methods

In this retrospective cohort analysis, we accurately diagnosed 42 cases of nephrotic IgAN (4.4%) from 954 IgAN patients, according to the Oxford classification. We analyzed the clinical and histological data, prognosis, and response to steroid therapy.

Results

In nephrotic IgAN, mean estimated glomerular filtration rate (eGFR) was 51.1?±?24.6?ml/min, proteinuria was 5.71?±?2.56?g/day, and urinary red blood cells were 51.0?±?37.8 high power field. Both active and chronic histological lesions were observed. Cumulative renal survival rate was significantly lower in nephrotic IgAN than in non-nephrotic IgAN (the control group consisted of 47 non-nephrotic IgAN patients diagnosed between 1995 and 1996) (log-rank test: P?Conclusion Nephrotic IgAN is a very severe form of IgAN, with renal dysfunction, massive hematuria, and active and chronic histopathological lesions. Renal outcome is severe; however, steroid therapy can improve prognosis in cases with higher eGFR and lower T-grade, according to the Oxford classification.     

Comparison of long-term follow-up outcomes between multiple-drugs combination therapy and tonsillectomy pulse therapy for pediatric IgA nephropathy

Background

To clarify the long-term efficacy of multiple-drugs combination therapy (PWDM) and tonsillectomy pulse therapy (TPT) for pediatric IgA nephropathy (IgAN), we retrospectively evaluated the clinical and laboratory findings as well as the prognosis for IgAN patients treated with each treatment at long-term follow-up.

Methods

We collected data on 61 children who had been diagnosed with severe IgAN. The children were retrospectively divided into two groups. Group 1 consisted of 44 severe IgAN children treated with PWDM, and Group 2 consisted of 17 severe IgAN children treated with TPT. The clinical features, pathological findings, and prognosis were analyzed for both groups.

Results

The mean urinary protein excretion, serum creatinine, IgA levels, MESTCG scores, and percentage of glomeruli showing crescents in both groups at the second renal biopsy were lower than those at the first renal biopsy. At the time of the second biopsy, the IgA level in Group 2 was lower than that in Group 1; however, there were no significant differences in the mean urinary protein excretion, frequency of hematuria, serum albumin, creatinine, or e-GFR between the two groups. At the most recent follow-up, there were no significant differences in prognosis between the groups.

Conclusions

Our study suggested that PWDM and TPT are effective in ameliorating urinary abnormalities and improving the long-term outcome of pediatric IgAN.

     

Study of tonsillectomy for IgA nephropathy patients: short- and longer-term observation

Objective

We observed serum parameters and urinary findings of IgA nephropathy (IgAN) patients in the short and longer time after tonsillectomy, to provide evidences to clarify the role of tonsils in the pathogenesis of IgAN and the feasibility of tonsillectomy for IgAN patients.

Methods

For the short-term study, 19 patients with both IgAN and chronic tonsillitis (group A) and 19 patients with chronic tonsillitis (group B) were performed bilateral tonsillectomy and 19 healthy people as normal controls (group C). Another 115 patients with IgAN and chronic tonsillitis including 61 patients for tonsillectomy combined with drug therapy and 54 for drug therapy alone followed up for 12 months.

Results

Fourteen patients of group A showed a deterioration of urinary findings, while only 2 patients of group B showed deterioration (P < 0.01). Both serum IgA and IgA1 levels were significantly higher in group A than that in group B or group C (P < 0.05, respectively). Levels of serum IgA and IgA1 of group A increased after tonsillectomy and did not increase instantly, but increased at day 3, then decreased at day 5. Both serum IgA and IgA1 levels were positively related to urinary red blood cell count (P < 0.01, r _s = 0.362, r _s = 0.347, respectively). For longer-term study, urinary findings of IgAN patients underwent tonsillectomy were improved significantly than that of patients without tonsillectomy (P < 0.05).

Conclusion

Tonsils play an important role in the development of IgAN, and tonsillectomy may be a feasible treatment method for IgAN patients with chronic tonsillitis.     

Overweight and obesity accelerate the progression of IgA nephropathy: prognostic utility of a combination of BMI and histopathological parameters

Background

Although more than 40?years have passed since IgA nephropathy (IgAN) was first reported, predicting the renal outcome of individual IgAN patients remains difficult. Emerging epidemiologic evidence indicates that overweight and obesity are risk factors for end-stage renal disease. We aimed to elucidate the outcome of overweight IgAN patients and improve our ability to predict the progression of IgAN based on a combination of body mass index (BMI) and histopathological parameters, including maximal glomerular area (Max GA).

Methods

Forty-three adult IgAN patients whose estimated glomerular filtration rate was ≥50?ml/min/1.73?m² were enrolled in this study. Renal biopsy specimens were evaluated according to the Oxford classification of IgAN. A Kaplan–Meier analysis and the multivariate Cox proportional hazards method were used to evaluate 10-year kidney survival and the impact of covariates. The ability of factors to predict the progression of IgAN was evaluated by their diagnostic odds ratio (DOR).

Results

A BMI ≥25?kg/m² was found to be an independent predictor of a ≥1.5-fold increase in serum creatinine value (DOR 7.4). The combination of BMI ≥25?kg/m², Max GA ≥42,900?μm², and presence of mesangial hypercellularity (Oxford M1) optimally raised predictive power for disease progression of IgAN (DOR 26.0).

Conclusion

A combination of BMI ≥25?kg/m², the Oxford classification M1, and a Max GA ≥42,900?μm² can serve as a predictor of long-term renal outcome of IgAN.     

Clinical significance of IgG deposition in the glomerular mesangial area in patients with IgA nephropathy

Background

Immunoglobulin (Ig) A nephropathy (IgAN) is characterized by mesangial deposits of IgA1 and C3, often with co-deposits of IgG. We attempted to clarify the clinical significance of mesangial IgG deposition in patients with IgAN.

Methods

We retrospectively reviewed 57 patients who were diagnosed with IgAN on the basis of pathological examination of renal biopsy specimens obtained between October 2006 and December 2010. Subjects were divided into two groups: IgA+IgG deposition (IgA-IgG) group (n = 29) and IgA deposition alone (IgA) group (n = 28). The study outcome was complete remission (CR), defined as negative proteinuria by dipstick urinalysis and urinary erythrocytes of less than 1–4/high-power field.

Results

Proteinuria was greater in the IgA-IgG group than the IgA group (1.1 ± 0.8 vs. 0.7 ± 0.6 g/day, Mann–Whitney U test, P = 0.042). Capillary wall IgA deposits were noted more frequently in the IgA-IgG group than the IgA group (59 vs. 11 %, Fisher’s exact test, P = 0.014). During the median follow-up period of 33.3 months (range 6–55 months) in the 57 patients, we observed CR in 24 cases (42.1 %). After the start of treatment, urinary abnormalities disappeared earlier in the IgA group than in the IgA-IgG group (log rank test, P = 0.012). Cox’s regression model showed that IgG deposition reduced the hazard ratio for CR (hazard ratio 0.35; 95 % confidence interval 0.14–0.82, P = 0.014). Therefore, IgG deposition is a risk factor for persistent urinary abnormalities.

Conclusion

Mesangial IgG deposition is associated with more severe clinical features in patients with IgAN.     

The clinical relevance of plasma CD147/basigin in biopsy-proven kidney diseases

Background

Precise understanding of kidney disease activity is needed to design therapeutic strategies. CD147/basigin is involved in the pathogenesis of acute kidney injury and renal fibrosis through inflammatory cell infiltration. The present study examined the clinical relevance of CD147 in biopsy-proven kidney diseases that lead to the progression of chronic kidney disease.

Methods

Kidney biopsy specimens and plasma and urine samples were obtained from patients with kidney diseases, including IgA nephropathy (IgAN), Henoch–Schönlein purpura nephritis (HSPN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), who underwent renal biopsy between 2011 and 2014. Plasma and urinary CD147 levels were measured and evaluated for their ability to reflect histological features. Disease activity of IgAN tissues was evaluated according to the Oxford classification and the Japanese histological grading system.

Results

In biopsy tissues, CD147 induction was detected in injured lesions representing renal inflammation. Plasma CD147 values correlated with eGFR in patients with inflammation-related kidney diseases such as IgAN, HSPN, and DKD. Particularly in IgAN patients, plasma CD147 levels were correlated with injured regions comprising more than 50% of glomeruli or with tubular atrophy/interstitial injury in biopsy tissues. Proteinuria showed a closer correlation with urinary values of CD147 and L-FABP. Of note, plasma and urinary CD147 levels showed a strong correlation with eGFR or proteinuria, respectively, only in DKD patients.

Conclusion

Evaluation of plasma and urinary CD147 levels might provide key insights for the understanding of the activity of various kidney diseases.

     

Clinicopathological significance of monoclonal IgA deposition in patients with IgA nephropathy

Background

Clinicopathological significance of monoclonal IgA deposition and its relation to bone marrow abnormalities in IgA nephropathy (IgAN) remains unclear.

Methods

We retrospectively investigated the prevalence and clinicopathological significance of monoclonal IgA deposition in 65 patients with IgAN. Serum-free light chain ratio, and urinary Bence Jones protein were also measured.

Results

Thirty-nine percent of patients were men, median age was 40 and median observation period was 31 months. Five patients (Group M) showed monoclonal IgA lambda deposition and one showed monoclonal IgA kappa deposition. Fifty-nine patients (Group P) showed polyclonal IgA deposition. There were no significant differences in the degree of proteinuria, hematuria and renal function between Group M and Group P. Total protein and albumin were significantly lower in Group M than in Group P. According to the Oxford classification, the percentage of patients with M1 was significantly higher in Group M than in Group P. One patient in Group P showed serum monoclonal IgG lambda. No patient showed abnormal serum-free light chain ratio. Seventy-five percent in Group M and 42 % in Group P were treated with steroid. Three patients in Group P progressed to end-stage renal disease (ESRD). The frequency of disappearance of proteinuria or hematuria and progression to ESRD was not different between the groups.

Conclusions

The prevalence of monoclonal IgA deposition was 9.2 %. Although some parameters differed between the groups, renal outcome were similar. Thus, IgAN with monoclonal IgA deposition seems not to be different entity from those with polyclonal IgA deposition.

     

Comparison of clinicopathological features between children and adults with IgA nephropathy

Background

IgA nephropathy (IgAN) is prevalent among both children and adults. Illumination of the differences between them is important for clinical doctors.

Methods

We retrospectively compared clinicopathological features in 110 children and 908 adults with IgAN.

Results

The male to female ratio was 1.62:1 in children and 0.85:1 in adults. Most patients lacked triggers, but IgAN was preceded by upper respiratory infection (URI) in 45.5% of children and 20.2% of adults. Gross hematuria was the most common initial symptom in children (53.6%), especially in those associated with URI (82.0%), while other symptoms and abnormal laboratory parameters were more common in adults. Estimated glomerular filtration rate (eGFR) was higher in children than in adults. Co-deposition of IgA and C3 were found in 50.9% of children, while IgA deposit was often accompanied by two or more immune complexes in adults. The frequency of subclass I was significantly higher in children than in adults. Mild histological lesions were more common in pediatric IgAN patients associated with URI than other patients.

Conclusions

Pediatric patients showed relatively mild clinical manifestations and histological lesions compared with adult patients. URI was the most important trigger for IgAN, particularly in children. IgAN associated with URI was relatively mild.     

The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients

Background

The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN).

Methods

A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine.

Results

In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC.

Conclusions

The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

     

Mycophenolic acid reverses IgA1 aberrant glycosylation through up-regulating Cosmc expression in IgA nephropathy

Objective

Impaired core I β3-Gal-T-specific molecular chaperone (Cosmc) expression-caused IgA₁ aberrant O-glycosylation is one of the main pathogeneses of IgA nephropathy (IgAN).This study tried to elucidate whether mycophenolic acid (MPA) could up-regulate Cosmc expression of peripheral lymphocytes in IgAN patients and reverse the dys-O-glycosylation.

Method

Peripheral lymphocytes of eighteen IgAN patients and twelve normal controls were isolated and cultured for 3–7 days with or without lipopolysaccharide (LPS) and MPA. Cosmc mRNA and protein expression levels were measured by real-time RT-PCR and western blot. IgA₁ and O-glycosylation level were determined by enzyme-linked immunosorbent assay (ELISA) and VV lectin-binding test. Correlation analysis was performed between Cosmc expression levels and IgA₁ O-glycosylation level.

Results

Cosmc mRNA expression and IgA₁ O-glycosylation level in IgAN patients were significantly lower than normal controls. Treatment of LPS could obviously inhibit the Cosmc expression and increase the IgA₁ secretion in peripheral lymphocytes of IgAN patients, which resulted in a significantly increase in IgA₁ aberrant glycosylation level. Addition of MPA could significantly increase the Cosmc expression level along with a decrease in IgA₁ secretion, leading to a reverse of aberrant glycosylation. A significant positive correlation between the Cosmc expression and IgA₁ O-glycosylation level was noticed.

Conclusion

MPA can up-regulate the Cosmc expression and reverse the IgA₁ aberrant O-glycosylation level in peripheral lymphocytes of IgAN patients, which might be the underlying mechanism of mycophenolate mofetil (MMF) therapy used in treating IgAN.     

The predictive value of attenuated proteinuria at 1 year after steroid therapy for renal survival in patients with IgA nephropathy

Background

The relationship between the urinary protein excretion (UPE) initially achieved after steroid therapy and the long-term renal outcome of IgA nephropathy (IgAN) has not been clarified. We investigated the threshold UPE at 1 year after steroid therapy which predicts a favorable renal survival.

Methods

We enrolled 141 IgAN patients who received 6 months of steroid therapy. The endpoint was defined as a 50 % increase in serum creatinine from baseline. The spline model was used to define the threshold UPE predicting renal survival.

Results

Thirteen patients (9.2 %) reached the endpoint at a median follow-up of 3.8 years. When evaluating the relative hazard ratio (HR) of the UPE at 1 year for the endpoint, we found an inflection point at 0.40 g/day on the spline curve. The multivariate Cox model revealed that, in addition to the Disappeared category of UPE (range <0.30 g/day), the Mild category (range 0.30–0.39 g/day) was associated with more reduced risk of the endpoint [HR 0.02, 95 % confidence intervals (CI) 0.00–0.29] relative to the Severe category (range ≥1.00 g/day), whereas the Moderate category (range 0.40–0.99 g/day) was not. The estimated glomerular filtration rate <60 ml/min/1.73 m² was also an independent predictor of the endpoint. When renal survival was adjusted with pathological parameters in the Cox model, UPE <0.40 g/day was still an independent favorable predictor (HR 0.08, 95 % CI 0.01–0.45).

Conclusions

In IgAN patients receiving 6 months of steroid therapy, the achievement of proteinuria <0.4 g/day at 1 year could be a therapeutic indicator for a favorable renal outcome.     

Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy

Aim

Trefoil factor 3 (TFF3) is a small peptide that is involved in mucosal protection. TFF3 is widely expressed in multiple tissues including kidney tissue. Previous studies have reported that the levels of urinary TFF3 are significantly increased in patients with chronic kidney disease. The aim of this study is to detect the TFF3 mRNA in kidney and elucidate the relationship between renal TFF3 mRNA and tubulointerstitial fibrosis in IgA nephropathy (IgAN).

Methods

We investigated the renal mRNA expression of TFF3 by real‐time PCR analysis in biopsy specimens from patients with IgAN, other glomerulonephritis (OGN) and minor glomerular abnormalities (MGA). We also determined the renal localization of TFF3 and the levels of urinary TFF3 by immunostaining and ELISA, respectively.

Results

The renal TFF3 mRNA expression was significantly associated with the urinary TFF3 secretion and the tubulointerstitial fibrosis score in the IgAN group alone. Immunostaining of the renal specimen of IgAN patients revealed that TFF3 is located in the renal tubular epithelial cells. The locations were almost the same as those that showed uromodulin positivity; specifically, the thick ascending limb (TAL) of the loop of Henle and the early portion of the distal tubule. The urinary TFF3 levels were positively correlated with the levels of urinary biomarkers of tubulointerstitial injury in such patients.

Conclusion

Renal TFF3 mRNA is associated with renal tubulointerstitial fibrosis in IgAN patients. The TFF3 located in the renal tubular epithelial cells may play a role in the progression of tubulointerstitial fibrosis in IgAN patients.     

Tonsillitis exacerbates renal injury in IgA nephropathy through promoting Th22 cells chemotaxis

Background

Tonsillitis can promote the progression of IgA nephropathy (IgAN) by aggravating immunopathologic response. Th22 cell disorder is involved in the pathogenesis of IgAN with tonsillitis. This study was determined to explore the possible mechanism of IgAN with tonsillitis underlying Th22 cell chemotaxis response to the effect of CCL20, CCL22, and CCL27.

Methods

This research was conducted on 65 subjects including 16 healthy controls (HC group), 5 patients with  renal carcinoma (HTC group) and 44 patients with IgAN between 2015 and 2016. According to clinical symptoms and results of throat swab culture, patients with IgAN were divided into two groups: IgAN with tonsillitis (IgAN + tonsillitis, n = 14) and IgAN patients without tonsillitis (IgAN, n = 30). Distribution of Th22 cells in IgAN patients was determined. The expression of CCL20, CCL22, and CCL27 in both peripheral blood and kidneys of IgAN patients was investigated. Severity of pathological lesions in IgAN patients was analyzed. Coculture assay and transwell assay were performed to explore the impacts of human mesangial cells (HMC) on Th22 cell chemotaxis and Th22 cell local accumulation under hemolytic streptococcus (HS) infection.

Results

Th22 cell percentages in IgAN patients increased compared with healthy controls. This increased Th22 cell percentage was positively correlated with the renal lesions of IgAN patients. Correspondingly, the expression of CCL20, CCL22, and CCL27 in renal tissue increased in IgAN patients. Tonsillitis exacerbated these overrepresentations of Th22 cells and chemokines. It was found that HMC could produce CCL20, CCL22, and CCL27. The supernatant of HMC was chemotactic for Th22 cells. This activity of HMC was stimulated by HS infection, whereas treatment of anti-CCL20, anti-CCL22, and anti-CCL27 antibodies partly blocked this chemoattractant effect of HMC.

Conclusions

Tonsil infection may aggravate the renal pathological lesions of IgAN by exacerbating Th22 cell accumulation. Our data suggested a collaboration between HMC and Th22 cells in IgAN with tonsillitis underlying the effects of CCL20, CCL22, and CCL27.

     

Spontaneous remission in children with IgA nephropathy

Background

Some patients with IgA nephropathy (IgAN) achieve spontaneous remission even when not receiving medication. However, details on such remissions remain unknown. The aim of our study was to clarify this information in the clinical setting of childhood IgAN with minor glomerular abnormalities or focal mesangial proliferation (MGA/FMP).

Methods

This study was a retrospective analysis of 96 children with MGA/FMP who did not receive medication from among the 555 patients with newly diagnosed childhood IgAN treated between January 1972 and December 2000. The Kaplan?CMeier method and Cox proportional hazard model were used for the analysis.

Results

Of the 96 pediatric patients who did not receive medication, 57 (59.4?%) achieved spontaneous remission. The cumulative spontaneous remission rates among these patients were 57.5? and 77.4 % at 5?and 10 years, respectively, from onset. The mean time from onset to remission was 5.9?±?0.4?years. Clinical and histological findings were similar between the remission and non-remission groups. Of the 57 patients with spontaneous remissions, ten (17.5?%) also developed a recurrence of urinary abnormalities. The cumulative recurrence-free rates were 79.9?and 67.9 % at 5 and 10?years, respectively, after remission.

Conclusions

The spontaneous remission rate in childhood IgAN with MGA/FMP was higher than expected. Our results suggest that physicians should consider the potential for spontaneous remission and refrain from very aggressive treatment in IgAN patients with MGA/FMP.     

Urinary NGAL and KIM-1: potential association with histopathologic features in patients with renal cell carcinoma

Purpose

NGAL and KIM-1 are suggested to play a key role in the carcinogenesis and progression of renal cell carcinoma. Attention is currently focused on the potential use of the urinary level of NGAL and KIM-1(uNGAL and uKIM-1, respectively) in making an early diagnosis, establishing a prognosis and determination of the histologic characteristics.

Methods

Forty-six patients underwent surgical treatment for renal lesions (n = 37) and for non-functioning kidney (n = 9). uNGAL and uKIM-1 levels were evaluated for clear cell, papillary and chromophobe subtypes of renal cancer patient and also for the control patients. The concentrations were determined by ELISA.

Results

uNGAL and uKIM-1 in the control group were not significantly different from those of the patients with kidney cancer. There was no association between tumor size or histologic grade and the uNGAL and uKIM-1 levels. All patients with papillary type RCC had KIM-1 level below 2 ng/mgUcr and uNGAL concentration above 50 ng/mgUcr. Using the same threshold values enables prediction of 100 % of patients with chromophobe subtype; 91.6 % of the patients with clear cell histology have uNGAL concentration below 50 ng/mgUcr and KIM-1 concentration below 5 ng/mgUce.

Conclusion

Combined analysis of uNGAL and uKIM-1 allowed high prediction rate of the histologic subtype of the radiographic-detected masses among cases with kidney cancer. These biomarkers may enable to select the proper therapeutic agents in cases with metastatic disease without the need of pretreatment biopsy.     

Proposal of remission criteria for IgA nephropathy

Background

The remission criteria of immunoglobulin A (IgA) nephropathy have varied depending on the clinical study. Therefore, nephrologists cannot make a uniform assessment of treatment outcomes and the standardization of explanations of the condition is difficult in patients with IgA nephropathy. This study aims to propose clinical remission criteria for IgA nephropathy based on a nationwide opinion survey in Japan regarding IgA nephropathy remission/relapse.

Method

This nationwide survey was sent to 312 teaching facilities of the Japanese Society of Nephrology by Progressive Renal Disease Research, Research on Intractable Disease, from the Ministry of Health, Labour and Welfare of Japan.

Results

Valid answers were obtained from 193 facilities (61.9 %) (136 internal medicine facilities and 57 pediatric facilities), of which 134 (69.4 %) thought that both hematuria and proteinuria should be used in the remission standards. Approximately half of the survey respondents shared the opinion on standards of negative results for hematuria and proteinuria and the duration and frequency of these conditions.

Conclusion

In this paper, we propose a standardized set of criteria for defining IgA nephropathy remission: three consecutive negative results over a 6-month period in urinary occult blood tests; urinary sediment red blood cell count of <5/high-power field (hematuria remission); and urinary protein of <0.3 g/day (g/g Cr; proteinuria remission). Clinical remission is defined as cases with both hematuria and proteinuria remission. These consensus-based remission criteria should be verified in future studies. In the meantime, they may be useful in predicting therapeutic outcome in cases of IgA nephropathy.     

CD147/basigin reflects renal dysfunction in patients with acute kidney injury

Background

Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI.

Methods

Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary l-fatty acid-binding protein (l-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining.

Results

In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary l-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary l-FABP.

Conclusion

CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication.     

Complete remission within 2 years predicts a good prognosis after methylprednisolone pulse therapy in patients with IgA nephropathy

Background

Pozzi et al. reported the effectiveness of steroid pulse therapy (Pozzi??s regimen) in IgA nephropathy (IgAN). The present study was performed to clarify the predictive factors for IgAN patients treated with Pozzi??s regimen.

Methods

One hundred nine IgAN patients treated by Pozzi??s regimen were observed for up to 112.6 (median 39.7) months, and remission of proteinuria (PR) and disappearance of urinary abnormalities [complete remission (CR)] after Pozzi??s regimen were analyzed. Predictive factors for the glomerular filtration rate (GFR) slopes for up to 5?years were analyzed among 81 patients who were observed for at least 2?years. The outcome of a 50?% increase in sCr was compared between the CR and non-CR groups within 2?years.

Results

Cumulative PR and CR rates increased rapidly until 2?years (54.5 and 46.8?% at 2?years), and then slowly but steadily up to 6?years (72.8 and 66.4?% at 6?years). Baseline characteristics of the CR and non-CR groups within 2?years were similar except for proteinuria. GFR slope was steeper in the non-CR group than in the CR group (?2.44?±?5.12 vs. ?0.32?±?3.34?ml/min/1.73?m²/year). On multivariate analysis, sex and CR within 2?years were associated with GFR slope. Kaplan-Meier analysis demonstrated a better survival rate in CR group patients without a 50?% increase in sCr (p?=?0.024).

Conclusions

Among IgAN patients treated with Pozzi??s regimen, CR within 2?years predicts a good prognosis.