Early prediction of IgA nephropathy progression: proteinuria and AOPP are strong prognostic markers

BACKGROUND: Inflammation and oxidative stress have been incriminated in the pathogenesis of IgA nephropathy (IgAN). The aim of the present study was to assess whether markers reflecting these pathophysiologic processes, namely C-reactive protein (CRP) and advanced oxidation protein products (AOPP), would allow-in conjunction with clinical and histopathologic parameters-to predict disease progression. METHODS: Between 1994 and 1997, 120 adult patients with biopsy-proven IgAN were included in a prospective cohort study, and followed until the end of 2002 or start of dialysis. In every patient, we determined plasma levels of CRP and AOPP. These parameters were included, together with clinical data, in a multivariate Cox proportional hazard regression analysis, with halving of baseline creatinine clearance as the primary renal end point. RESULTS: A total of 51 patients reached the renal end point, including 30 who had to start dialysis. With multivariate analysis, the most potent independent risk factors of poor renal outcome were proteinuria > or =1 g/day [proportional hazard risk (HR) = 23.7, P= 0.0001], hypertension (HR = 8.13, P= 0.008), and AOPP plasma level (HR = 1.09 per 10 micromol/L, P= 0.042), whereas angiotensin II inhibitors were protective (HR = 0.19, P= 0.001). CONCLUSION: Our data support the role of oxidative stress in the pathogenesis of IgAN and suggest that patients with proteinuria > or =1 g/day should be eligible for early implemented antioxidant and/or anti-inflammatory therapeutic strategies, with AOPP plasma level as a surrogate marker to evaluate their effects.     

肾性血管活性因子与糖尿病肾病研究进展

AngⅡ具有多种生物学效应,包括激活细胞内第二信使、转录因子、细胞外基质蛋白、各种生长因子和细胞因子,从而导致糖尿病肾脏发生结构和功能改变。但RAS阻断剂却不能阻止糖尿病人进展到终末期肾病。评估其与AngⅡ相似且功能独特的血管活性因子将有助于了解它们在糖尿病肾病进展中的可能作用。进一步研究包括血管肽酶、内皮素、尾加压素Ⅱ及RAS等在内的血管活性物质可能为治疗糖尿病肾病提供新的策略。     

影响原发性IgA肾病预后的临床病理因素研究进展

IgA肾病(IgA Nephropathy,IgAN)具有慢性进展性质,需要识别该病进展的标志和预后的影响因素.现已明确肾活检时的血肌酐水平、持续性蛋白尿、高血压对预测IgAN预后的价值最大.广泛的肾小球硬化及/或肾间质纤维化是最强的独立的预测疾病进展的病理学参数.新近提出的病理评分系统能独立于临床地反映IgAN预后.还有研究显示结合多个参数(特别是临床病理结合)可更好地预测疾病进展和判断预后.     

Transitional cell carcinoma of the ureter: prognostic factors influencing progression and survival

OBJECTIVES: We retrospectively evaluated prognostic factors for progression-free and disease-specific survival in a large cohort of patients with transitional cell carcinoma (TCC) of the ureter. METHODS: A single-centre series of 145 consecutive patients treated with partial resection of the ureter or nephroureterectomy between 1975 and 2004 was evaluated. Median follow-up was 96 mo. Routine preoperative laboratory parameters as well as clinical and tumour-specific data were assessed. Univariate and multivariate statistical analyses were performed. RESULTS: Five-year disease-specific survival ranged from 96.1% for stages pTa to 28.6% for pT4. Grade1 tumours were associated with 5-yr disease-specific survival rates of 100% compared with 84% for G2, and 51.9% for G3 tumours, respectively. Univariate analyses identified pT stage and grade, tumour diameter, cM and pN categories, weight loss, the presence of synchronous tumour in the renal pelvis as well as elevated levels for humoral factors such as serum alkaline phosphatase (AP), white blood cell (WBC) count, platelet count, gamma-glutamyl transferase, creatinin, and blood urea nitrogen as prognostic factors. In multivariate analyses, tumour grade and WBC counts were predictive for low progression-free survival rates, whilst simultaneous tumour in the renal pelvis, high AP levels, and WBC counts were correlated with worse disease-specific survival. CONCLUSIONS: Our retrospective analysis provides clinical factors to identify patients with TCC of the ureter at high risk for progression and death of disease. Interestingly, humoral factors such as elevated serum AP levels and high WBC counts were demonstrated to be of paramount prognostic significance besides tumour stage, grade and multifocality.     

Evaluating the clinical course and prognostic factors of posttransplantation immunoglobulin A nephropathy

INTRODUCTION: Previous reports have suggested that posttransplantation immunoglobulin (Ig) A nephropathy displays a relatively benign course, hardly ever affecting graft function. However, more recent studies with longer follow-up have shown that posttransplantation IgA nephropathy may be a significant contributor to graft loss. Additionally, there may be other clinical or pathological factors that affect long-term graft outcome. We retrospectively analyzed 30 kidney transplant recipients with biopsy-proven IgA nephropathy in their allografts to determine the clinical course and prognostic factors in posttransplantation IgA nephropathy. The median duration of follow-up was 36 months (range, 1 month-17 years). The median onset of IgA nephropathy was 33.6 months posttransplantation (range, 5 days-103 months). The most common presentation was an abnormal urine examination (96.6%). Fifteen (50%) displayed microscopic hematuria with proteinuria more than 1 g/d. Fifteen patients (50%) lost their grafts at a median time of 24 months after the onset of disease (range, 1-93 months). Allograft loss was associated with a high serum creatinine level at the time of diagnosis (3.68 +/- 2.23 vs 1.79 +/- 0.34 mg/dL; P = .006), a greater level of proteinuria at the time of diagnosis (2.43 +/- 0.76 vs 1.29 +/- 1.07 g/d; P = .003), and more than 50% extracapillary proliferation (P = .05). Fibrinoid necrosis on allograft pathology impacted 1-year allograft survival (P = .025). CONCLUSION: Posttransplantation IgA nephropathy worsens allograft outcomes among patients with increased serum creatinine level or significant proteinuria at presentation or significant glomerular inflammation and/or tubulointerstitial damage.     

Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy.

BACKGROUND: The prognosis of IgA nephropathy (IgAN) is variable and about 10-20% of patients progress to end-stage renal disease (ESRD) in 10 years. Hypertension, proteinuria and renal insufficiency at the time of diagnosis are risk factors associated with poor prognosis. Lipid abnormalities may have a role in the progression of glomerulonephritides, and glomerulosclerosis and atherosclerosis may have similar pathophysiological mechanisms. We therefore evaluated factors associated with cardiovascular diseases, especially hypercholesterolaemia, hypertriglyceridaemia, and hyperuricaemia, as predictors of the progression of IgAN. METHODS: A total of 223 patients with IgAN (141 men, 82 women; median age 41 years, range 8-78 years) were studied. The following parameters were recorded at the time of renal biopsy: presence of hypertension or diabetes, smoking habits, body mass index (BMI), serum creatinine, total and HDL-cholesterol, triglycerides, and urate and 24-h urinary protein excretion. The patients were followed up for 0.2-17 years (median 10 years) with respect to progression of renal disease defined as elevation of serum creatinine above 125 micromol/l in men or 105 micromol/l in women, and over 20% elevation from baseline. RESULTS: Forty-one patients (18%) showed progression. Hypertriglyceridaemia and hyperuricaemia were significantly more common at the time of renal biopsy in patients with progressive than in those with stable disease. In patients with normal renal function at the time of diagnosis initial hypertriglyceridaemia, hyperuricaemia, hypertension and proteinuria were independent risk factors for progression of IgAN in the Cox regression hazard model. CONCLUSIONS: Our results show that hypertriglyceridaemia and hyperuricaemia at the time of diagnosis are important, previously underestimated predictors of poor outcome in IgAN, although causality between these factors and progression cannot be inferred from the present study.     

The influence of familial factors on the progression of IgA nephropathy

Background. Vascular risk factors in first degree relatives of patients with insulin dependant diabetes mellitus are known to increase the risk of that patient developing diabetic nephropathy. We explored the influence of vascular risk factors in first degree relatives on patients with stable (serum creatinine <150 &mgr;mol/l for >5 years) and progressive (serum creatinine >200 &mgr;mol/l, and >150% serum creatinine at presentation, after minimum follow-up at 2 years) IgA nephropathy (IgAN). Methods. We compared sodium-lithium countertransport activity (SLC Vmax), plasma lipoprotein(a) and von Willebrand factor (vWf) concentrations, incidence of vascular disease, and incidence of hypertension in 37 first degree relatives of 23 patients with stable IgAN and 33 first degree relatives of 17 patients with progressive IgAN. The two groups of relatives were comparable with respect to other risk factors: age, smoking, blood pressure, and plasma glucose, creatinine, cholesterol and triglyceride concentrations. Results. SLC Vmax was higher in relatives of stable patients (mean 0.37 mmol/h/l RBC [S.D. 0.18] vs 0.30 [S.D. 0.09]; P=0.034 two-sample t-test). There was no difference between the relatives of stable and progressive patients in plasma lipoprotein(a) concentration (median 11.5 mg/l vs 13.0: P=0.45; 95% C.I. -12 to 3; Mann-Whitney test), plasma vWf concentration (149.4 IU/dl [S.D 55.6] vs. 163.2 IU/dl [S.D. 57.3]; P=0.31 two-sample t-test), or incidence of hypertension (13/37 [35.1%] vs 10/33 [30.3%]; &khgr;²=0.185; P=0.667). Relatives of patients with progressive IgAN had a slightly higher incidence of vascular disease (10/33 [30.3%] vs 8/37 [21.6%]; &khgr;²=0.688; P=0.407). Conclusions. Familial vascular risk may increase the likelihood of progressive renal failure in patients with IgAN but the influence is likely to be small and unrelated to the factors we measured. SLC Vmax was significantly higher in relatives of patients with stable disease which contrasts with data from other studies and is unexplained.     

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.     

IgA nephropathy. Evaluation of prognostic factors in patients with moderate disease

Previous studies of IgA nephropathy have demonstrated a number of prognostically significant clinical and pathological factors in groups of patients with the full histological spectrum of the disease. Whether these factors can be applied to a group of IgA nephropathy patients with disease of moderate degree is unknown. Forty patients (9 females, 31 males) with grade III IgA nephropathy (no more than 10% obsolete glomeruli and little or no interstitial fibrosis) were evaluated with respect to age, sex, degree of proteinuria, history of recurrent gross hematuria, hypertension, extent and type of segmental glomerulosclerosis, demonstration of IgG and/or IgM in deposits, presence of peripheral capillary deposits, whether or not there were crescents, and extent of vascular sclerosis. The mean age was 29.6 +/- (SD) 13.1 years. Sixteen patients presented with recurrent gross hematuria, and 24 had microscopic hematuria and proteinuria as the initial manifestation. Hypertension was seen in 5 patients. The mean serum creatinine concentration was 1.09 +/- 0.47 mg/dl (96.4 +/- 41.5 mumol/l), and the mean 24-hour urinary protein was 1.5 +/- 1.3 g. Nine patients had proteinuria greater than or equal to 2.0 g/24 h. Thirty-two patients demonstrated segmental glomerulosclerosis in their biopsies, 13 of which had more than 10% of the glomeruli involved. Seven patients developed established renal failure (Cr greater than or equal to 2.0 mg/dl; 176.8 mumol/l). The 60-and 100-month renal survival rates were 96 and 52%. Life table analysis disclosed that only the degree of proteinuria (greater than or equal to 2.0 g/24 h; p less than 0.05) and the extent of segmental glomerulosclerosis (p less than 0.025) were of prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multivariate analysis of prognostic factors and effect of treatment in patients with IgA nephropathy

BACKGROUND: Although the clinical and histological prognostic factors of IgA nephropathy have been investigated in detail, the value of treatment in terms of renal outcome is not well understood. METHODS: The authors examined data from 237 patients with IgA nephropathy (age 31.4+/-13.5 years, mean+/-SD) who had been followed-up for at least six months (follow-up periods, 62.3+/-45.5 months). The authors initially tested the significance of prognostic factors (age, sex, systolic blood pressure, proteinuria, serum creatinine, and histological severity) and treatment strategies (steroid therapy, renin-angiotensin system inhibitors and tonsillectomy) on renal outcome with univariate analysis, then evaluated the findings using the Cox proportional hazards model. RESULTS: Univariate and multivariate analyses showed that among the prognostic variables, a high level of serum creatinine at renal biopsy, large amounts of proteinuria, and extensive histological injury were significant risk factors for end-stage renal failure. Kaplan-Meier analysis showed that the renal survival rates associated with these factors were significantly poorer depending on their severity. Univariate analysis revealed that tonsillectomy was the only significant treatment that contributes to the maintenance of renal survival. Moreover, urinary abnormalities disappeared at a significantly higher frequency when patients were treated by tonsillectomy. The Cox proportional hazards model showed that steroid therapy independently contributed to improve renal prognosis in addition to tonsillectomy, and the hazard ratios were 0.26 (95% CI, 0.07 to 0.93) and 0.37 (95% CI, 0.14 to 0.99), respectively. CONCLUSION: Steroid therapy and tonsillectomy can independently improve renal outcome in patients with IgA nephropathy.     

Diabetic nephropathy: recent insights into the pathophysiology and the progression of diabetic nephropathy

Diabetes has become the single most frequent comorbid condition in patients admitted for renal replacement therapy. This is the result of a greater prevalence of type 2 diabetes and better survival of diabetic patients. Progress has been made in pinpointing the predisposition to diabetes on metabolic abnormalities of muscle mitochondrial metabolism, but the long sought genes predisposing to diabetes and to diabetic nephropathy have not yet been identified. Of great concern are experimental studies documenting that maternal hyperglycemia causes nephron underdosing in the offspring. Relevant to pathogenesis and treatment of diabetic nephropathy are, among others, recent insights that hyperglycemia sensitizes target organs to blood pressure-induced damage, and that local renin-angiotensin systems play an important role in genesis and progression of diabetic nephropathy.     

De novo degenerative lumbar scoliosis: a systematic review of prognostic factors for curve progression

Purpose

To identify prognostic factors for curve progression in de novo degenerative lumbar scoliosis (DNDLS) by performing a systematic review of the literature.

Methods

Studies were selected for inclusion following a systematic search in the bibliographic databases PubMed and EMBASE prior to September 2015 and hand searches of the reference lists of retrieved articles. Two authors independently assessed methodological quality. Data were extracted and presented according to a best evidence synthesis.

Results

The literature search generated a total of 2696 references. After removing duplicates and articles that did not meet inclusion criteria, 12 studies were included. Due to the lack of statistical analyses, pooling of data was not possible. Strong evidence indicates that increasing intervertebral disk degeneration, lateral vertebral translation ≥6 mm, and an intercrest line through L5 (rather than L4) are associated with DNDLS curve progression. Moderate evidence suggests that apical vertebral rotation Grade II or III is associated with curve progression. For the majority of other prognostic factors, we found limited, conflicting, or inconclusive evidence. Osteoporosis, a coronal Cobb angle <30°, lumbar lordosis, lateral osteophytes difference of ≥5 mm, and degenerative spondylolisthesis have not been shown to be risk factors. Clinical risk factors for progression were not identified.

Conclusions

This review shows strong evidence that increased intervertebral disk degeneration, an intercrest line through L5, and apical lateral vertebral translation ≥6 mm are associated with DNDLS curve progression. Moderate evidence was found for apical vertebral rotation (Grade II/III) as a risk factor for curve progression. These results, however, may not be directly applicable to the individual patient.

     

IgA nephropathy: markers of progression and clues to pathogenesis

The unpredictable progression of IgA nephropathy hinders its treatment. The correlation of renal dysfunction with the immunophenotype of leukocytic infiltrates revealed interstitial CD20(+) cells and tubular NKG7(+)(GMP-17(+))/CD8(+) intraepithelial cells as predictive markers of progression in early-phase IgA nephropathy. This suggests that adaptive and innate immune responses mediate progression.     

IgA nephropathy: prognostic significance of proteinuria and histological alterations

A retrospective study of 166 patients with IgA nephropathy was undertaken to clarify possible correlations between clinical and histological features, and the severity and prognosis of the disease. At the time of biopsy, impaired renal function, with creatinine clearance (Ccr) below 90 ml/min was found in 61 cases. At the final examination, after a mean follow-up period of 34 months, 82 patients had impaired renal function, 12 of these patients went into terminal renal failure requiring hemodialysis treatment. The presence of proteinuria of more than 1.0 g/day was closely correlated with impairment of renal function both at the time of biopsy and at the final observation. An unfavorable outcome was also anticipated in the presence of hypertension. In contrast, microhematuria, macrohematuria or high serum IgA levels did not appear to be related to the outcome. Histologically, sclerotic lesions such as mesangial or global sclerosis, interstitial fibrosis and tubular atrophy, and some active changes such as mesangial hypercellularity and tuft adhesion were more frequent and severe in patients with impaired renal function. Impressive localization of IgA and C3 in the mesangium as well as in capillary loops was observed more often in these patients. These results clearly indicate that IgA nephropathy may follow a slowly progressive course in about half of the patients, and that marked proteinuria and severe histological changes appear to correlate closely with an unfavorable course.     

Myofibroblasts and the progression of diabetic nephropathy

Background. The cellular mediators of progressive renal fibrosis in diabetic nephropathy remain unknown. Myofibroblasts have been implicated in the pathogenesis of experimental and clinical renal fibrosis. Their role in the progression of diabetic nephropathy is the subject of this study.Subjects and methods. We have studied by immunohistochemistry the expression of cytoskeletal proteins associated with the activation of myofibroblasts; &agr;-smooth-muscle actin (&agr;-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25 patients with diabetic nephropathy (5 patients with diabetic nephropathy (5 patients had a superimposed glomerulonephritis). Comparisons were made with normal tissue for three kidneys removed for renal-cell carcinoma. Correlations were studied between clinical and biochemical parameters with the expression renal cytoskeletal proteins. Results. In normal kidneys, cells expressing &agr;-SMA were confined to the vascular media and adventia while immunoreactive Vi was detected in glomerular epithelial cells. In diabetic kidneys, cells expressing &agr;-SMA were detected primarily in the renal interstitium and to a lesser extent in some glomeruli in association with mesangial proliferation. Vimentin immunostain decreased in glomeruli displaying diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity was noted in atrophic diabetic tubules and to a lesser extent in the interstitium. Desmin was not detected in either normal or diabetic kidneys. Close correlations were observed between the expression of renal cytoskeletal proteins and the progression of renal insufficiency. Interstitial &agr;-SMA proved to be a predictor of progressive diabetic nephropathy (R² for 1/serum Cr slope=0.608, P=0.00001). This predictive parameters; tubular atrophy (R²=0.477, P=0.00004) and interstitial fibrosis (R²=0.28, P=0.001). Conclusion. We have demonstrated in this study the neoexpression of cytoskeletal proteins within diabetic kidneys. This has allowed the identification of new predicting histological markers for the progression of diabetic nephropathy.     

Time series spinal radiographs as prognostic factors for scoliosis and progression of spinal deformities

The effectiveness of clinical measures to predict scoliotic progression is unclear. The objective of this study was to identify potential prognostic factors affecting scoliosis progression. Consecutive measurements (181) from 35 non-instrumented adolescent idiopathic scoliosis patients with at least two follow-up assessments were studied. Potential prognostic factors of gender, curve pattern, age, curve magnitude, apex location and lateral deviation and spinal growth were analyzed. Stable and progressed groups were compared (threshold: Cobb angle ≥5° or 10°) with sequential clinical data collected in 6-month intervals. Double curves progressed simultaneously or alternatively on curve regions. Age was not significantly different prior to and at maximal Cobb angle. Maximal Cobb angles were significantly correlated to initial Cobb angles (r = 0.81–0.98). Progressed males had larger initial Cobb angles than progressed females. Apex locations were higher in progressed than stable groups, and at least a half vertebra level higher in females than males. Maximal apex lateral deviations correlated significantly with the initial ones (r = 0.73–0.97) and moderately with maximal Cobb angles (r = 0.33–0.85). In the progressed groups, males had larger apex lateral deviations than females. Spinal growth did not relate to curve progression (r = −0.64 to +0.59) and was not significantly different between groups and genders. Scoliosis may dynamically progress between major and minor curves. Gender, curve magnitude, apex location and lateral deviation have stronger effects on scoliosis progression than age or spinal growth. Females with high apex locations may be expected to progress.