The product of duration and amount of proteinuria (proteinuria index) is a possible marker for glomerular and tubulointerstitial damage in IgA nephropathy

BACKGROUND/AIMS: IgA nephropathy (IgAN) is one of the major causes for chronic renal failure (CRF). Presence of massive proteinuria, hypertension, increased serum creatinine level and sclerotic histopathological changes of the glomerulus are known to be determinants for the progression of CRF. However, the relationships between duration of proteinuria/hematuria and histopathological changes, which may be correlated with the renal prognosis, have not been clarified. METHODS: A cross-sectional, univariate analysis of clinical parameters on the four glomerular and three tubulointerstitial histopathological grades in 57 untreated biopsy-proven IgAN patients (M/F = 32/25) was performed. RESULTS: The age at the time of renal biopsy (35.2 +/- 13.0 years; mean +/- SD), average duration of proteinuria (5.3 +/- 5.8 years), mean urinary protein excretion (0.99 +/- 1.22 g/day), serum creatinine (Cr 0.97 +/- 0.28 mg/dl), Cr clearance (Ccr 75.5 +/- 29.4 ml/min), and blood urea nitrogen (BUN 15.4 +/- 3.9 mg/dl) were well correlated with both histopathological grades. The product of duration (years) and urinary protein excretion (g/day) at the time of renal biopsy was more significantly correlated with glomerular and tubulointerstitial histopathological grades and serum Cr. CONCLUSION: The natural course of IgAN is steadily progressive depending on the duration and amount of proteinuria. The product of these two factors (proteinuria index) may be a useful predictor for glomerular and interstitial histopathological changes and the fate of renal function in IgAN.     

Treatment of severe Henoch–Schönlein and immunoglobulin A nephritis. A single center experience

Our aim was to report the effect of two treatment regimens in 43 cases of severe Henoch–Schönlein nephritis (HSN) and immunoglobulin A nephritis (IgAN) (24 HSN, 19 IgAN). Group A, 11 HSN and 7 IgAN, 88% with an International Study of Kidney Disease in Children (ISKDC) biopsy grade ≥ III and severe clinical features, were treated with corticosteroids, cyclophosphamide (CYC-P) and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB). Group B, 12 HSN and 13 IgAN, 72% with biopsy findings as above and 52% with severe clinical features, were treated with ACEi/ARB ± corticosteroids. The outcome classification was: (a) healthy; (b) mild proteinuria, normal glomerular filtration rate (GFR); (c) active renal disease; (d) chronic renal failure. Twenty-six patients had a good outcome (a?+?b). The 17 children with poor outcome (c?+?d) had lower GFR at onset and at follow-up, higher albumin excretion at follow-up, and higher percentage of segmental glomerulosclerosis in the renal biopsy, than those with good outcome. Treatment with corticosteroids, CYC-P and ACEi/ARB was effective in increasing GFR, reducing proteinuria and decreasing the disease activity index. The proteinuria had decreased at follow-up in both groups. In group A, GFR increased and histopathological activity index declined after treatment. The outcome did not differ between groups A and B. The effects of treatment did not differ between HSN and IgAN.     

血管紧张素Ⅱ受体拮抗剂对慢性肾衰竭大鼠肾小管上皮细胞增殖和转分化的影响

目的：探讨血管紧张素Ⅱ受体拮抗剂（ARB）losartan对慢性肾衰竭（CRF）大鼠肾小管上皮细胞增殖和转分化的影响。方法：Wistar大鼠随机分为假手术（Sham）组、模型（Nx）组、ARB小剂量（ARB15,losartan 15mg·kg^-1·d^-1灌胃）组、ARB大剂量（ARB150,losartan 150mg·kg^-1·d^-1灌胃）组。5/6肾切除制作CRF模型。12周后,观察各组肾功能、蛋白尿、肾重/体重（BW）、心脏重量/BW、肾脏病理变化,免疫组化观察肾脏胰岛素样生长因子-1（IGF-1）、α-平滑肌肌动蛋白（α-SMA）、Vimentin表达变化及增殖细胞核抗原（PCNA）阳性细胞数,TUNEL法观察细胞凋亡。结果：（1）Nx组大鼠Scr、BUN、24h尿蛋白定量、肾重/BW、心脏重量/BW均明显高于Sham组（P〈0.05）;ARB治疗后肾功能明显改善、蛋白尿减少、肾重/BW、心脏重量/BW降低（P〈0.05）。（2）Nx组大鼠肾组织有明显的肾小球硬化及肾小管间质损伤,肾小球硬化指数（GSI）及肾小管间质损伤指数（TII）均较Sham组明显增高;ARB治疗后GSI及TII均较Nx组降低（P〈0.05）。（3）与Sham组比较,Nx组肾间质IGF-1表达明显增加（P〈0.05）,ARB可明显减少IGF-1的表达（P〈0.05）。（4）Sham组肾组织可见α-SMA表达,肾间质无Vimentin表达;Nx组肾间质Vimentin及α-SMA表达增加（均P〈0.05）,ARB治疗后较Nx组两者表达减少（P〈0.05）。（5）Nx组TUNEL阳性细胞和PCNA阳性细胞均明显增加,ARB治疗对TUNEL阳性细胞无明显影响,但可明显减少PCNA阳性细胞数（P〈0.05）。结论：ARB可明显减轻CRF大鼠的肾损伤,该作用与抑制局部IGF-1表达和肾小管上皮细胞转分化以及改变细胞凋亡与增生的平衡有关。     

Angiotensin-converting enzyme genotype and outcome in pediatric IgA nephropathy

Angiotensin-converting enzyme (ACE) I/D polymorphism has been implicated as a genetic marker for progression of glomerular disease. Studies of ACE genotypes in adults with IgA nephropathy (IgAN) have yielded conflicting results. We performed ACE genotyping on 79 patients with IgAN diagnosed prior to age 18 years who had either progressed to end-stage renal disease (ESRD) or are now more than 5 years post biopsy. Mean follow-up was 14.8 years for those with normal renal function. Forty-three (54.4%) subjects had normal renal function and a normal urinalysis at last evaluation. Sixteen (20%) progressed to ESRD and 1 has chronic renal insufficiency. Kaplan-Meier survival curves for progression to ESRD did not differ significantly for the ACE DD, ID, and II genotype groups (P=0.095, log-rank test). By univariate analysis, presence of hypertension and degree of proteinuria at diagnosis, and unfavorable histology but not ACE genotype, was significantly associated with progression to ESRD. In the Cox proportional hazards model that included grade of proteinuria, the ACE D allele was a significant independent predictor of outcome with a hazard ratio of 2.37 (P=0.031). Our data, while inconclusive, suggest that the ACE D allele may associate with poor outcome in pediatric IgAN.     

Influence of clinical and histological features on actuarial renal survival in adult patients with idiopathic IgA nephropathy, membranous nephropathy, and membranoproliferative glomerulonephritis: survey of the recent literature.

The most recent studies, using the actuarial life-table technique, of the problem of long-term renal outcome and the factors that influence it in adult patients with one of the three most common types of chronic idiopathic immune complexes-mediated glomerulonephritis (IgA nephropathy [IgAN], membranous nephropathy [MN], and type I membranoproliferative glomerulonephritis [MPGN]) are reviewed. In the last decade, renal survival 10 years after onset has become similar to adult patients with idiopathic IgAN (80% to 87%) and idiopathic MN (75% to 83%), because of improvement of the renal survival of patients with MN. Renal survival at 10 years is worse for adult patients with idiopathic type I MPGN (60% to 64%). There is no substantial difference in the average renal survival times between different geographical regions, with the exception of a better prognosis for idiopathic MN in Japan. The presenting clinical factors that most strongly predict subsequent poor outcome are similar for the three types of glomerulonephritis and are rather nonspecific: (1) severe proteinuria, (2) impairment of renal function, and (3) arterial hypertension. As for the histological features, the most powerful predictor of subsequent progression in all three types of glomerulonephritis is tubulointerstitial damage, suggesting that a cell-mediated immune process believed to occur there may independently influence outcome in glomerular diseases.     

Epidemiology, major outcomes, risk factors, prevention and management of chronic kidney disease in China

Chronic kidney disease (CKD) is common in China. In residents older than 40 years in Beijing, China, 11.3% of subjects had at least one indicator of kidney damage. The primary cause of chronic renal failure in China was glomerulonephritis, which was followed by diabetic nephropathy and hypertensive nephrosclerosis. Renal failure, cardiovascular disease and infection were important complications. IgA nephropathy (IgAN) is the most common CKD in China. The prevalence of hypertension, intrarenal artery lesions and tubulointerstitial lesions in patients with IgAN at the time of renal biopsy was approximately 40, 55 and 85%, respectively. The genetic variation in Megsin confers susceptibility to IgAN in Chinese. The patients with SL/LL genotypes of the MUC20 gene, the 38AA genotype of uteroglobin and DD genotype of the angiotensin-converting enzyme gene had a higher risk of progression. Chinese prospective clinical trials showed that benazepril (BZ) conferred substantial renal benefits in patients with advanced renal insufficiency. The combined therapy with urokinase and BZ was more effective than with BZ alone in reducing proteinuria and protecting renal function in Chinese patients with severe IgAN. Lupus nephritis (LN) is a common form of secondary renal disease diagnosed by renal biopsy in China. Chinese multicenter clinical trials showed that mycophenolate mofetil or leflunomide combined with steroids was effective as induction therapy for proliferative LN.     

Severity of tubulointerstitial inflammation and prognosis in immunoglobulin A nephropathy

Many risk factors for progression in immunoglobulin A nephropathy (IgAN) have been found. We focused on renal leukocyte infiltrations and cytokines in IgAN. The subjects were 204 IgAN patients. Renal histopathological changes were semiquantitatively graded. Expression of tubulointerstitial Leukocyte common antigen (LCA), CD3, CD68, interleukin (IL)-1beta, and IL-10 was evaluated by immunohistochemistry. These parameters were correlated with progression of IgAN. The significance of these correlations was tested by a multivariate analysis. Glomerulosclerosis, tubular atrophy, interstitial inflammation, and hyaline arteriolosclerosis correlated with progression in all patients and also in patients with initially normal serum creatinine. Tubulointerstitial LCA, CD3, CD68, and IL-1beta expression correlated with progression. CD3 had the strongest correlation. In the multivariate analysis, tubulointerstitial CD3, hypertriglyceridemia, elevated serum creatinine concentration, and interstitial fibrosis were independently associated with progressive disease in all patients, and tubulointerstitial CD3 expression and hyaline arteriolosclerosis in patients with initially normal serum creatinine. We found parameters reflecting tubulointerstitial inflammation to predict deterioration of renal function in IgAN. This was also seen in patients whose serum creatinine was normal at the time of renal biopsy. Our findings show that, an immunohistochemical evaluation of tubulointerstitial inflammation seems to be a useful tool in determining the prognosis in IgAN.     

少量蛋白尿和（或）血尿IgA肾病临床病理分析

目的 了解表现为少量蛋白尿和（或）血尿IgA肾病（IgAN）患者的肾脏病理特征及其与临床表现的关系。 方法 对1993年1月至2009年10月肾活检确诊为IgAN,且表现为少量蛋白尿 （<1 g/24 h）和（或）血尿,Scr<133 μmol/L的患者的临床和病理资料进行回顾性分析。病理学分级参照Lee分级及Katafuchi半定量积分标准。应用多因素logistic回归法分析肾脏病理损伤的危险因素。 结果 符合入选标准共316例,男123例,女193例,肾穿时年龄（33.10±10.69）岁。蛋白尿伴血尿占84.5%、单纯血尿占7.6%、单纯蛋白尿占7.9%。16.5%患者伴有高血压。CKD1、2、3期分别占76.9%、20.9%和2.2%。Lee Ⅲ级及以上患者占31.3%。52.8%患者有不同程度肾小球硬化;20.3%伴新月体形成;22.5%伴小管萎缩;16.8%有间质纤维化;24.7%有血管病变。肾小球硬化积分与估算肾小球滤过率（eGFR）呈负相关;与蛋白尿及平均动脉压（MAP）呈正相关。肾小管间质病变积分与eGFR及血红蛋白(Hb)呈负相关;与尿蛋白量呈正相关。血管病变积分与MAP呈正相关;与eGFR呈负相关(均P < 0.05)。多因素logistic回归分析结果显示,肾活检时尿蛋白量（OR = 8.564,P < 0.01）、Scr（OR = 1.031,P< 0.01）及Hb（OR = 0.975,P < 0.01）是肾脏病理损伤（LeeⅢ级以上）的独立危险因素。 结论 部分表现为少量蛋白尿和（或）血尿IgAN患者的病理改变并不轻,且肾功能已减退。尿蛋白量、Scr、Hb是预测肾脏病理损伤程度的独立危险因素。肾活检对这些患者明确诊断、判断病情和预后、制定个体化治疗方案十分重要。     

Ca antagonist ameliorates glomerular injury via suppression of glomerular hypertrophy in spontaneously hypertensive rats

Summary: A study was conducted to determine whether calcium blockers (CCB) have renoprotective effects, and if so to elucidate the mechanisms of such effects.
A total of 30 uninephrectomized (UNX) spontaneously hypertensive rats (SHR), 5 weeks of age, were divided into three groups. Group 1 was fed a diet containing 0.01% manidipine and 8% NaCl, while groups 2 and 3 were fed diets containing only 8 and 0.5% NaCl, respectively. Feeding of these diets began 7 days after UNX (experimental day 0). Bodyweight, urinary protein /24 h, urinary sodium excretion/24 h, and food intake were measured at certain time intervals.
At time of death (day 9 or 21), estimations of inulin clearance (Cin) and morphological evaluations, determination of glomerular sclerosis index (GSI), tubulointerstitial index (TII) and glomerular volume were performed.
Urinary protein was significantly higher in groups 1 and 2 than in group 3 from day 7 onward, but did not differ between the former two groups. Cin in group 2 was higher than in groups 1 and 3 on day 9, but declined to lower levels than in groups 1 and 3 by day 21. There was no difference in Cin between group 1 and group 3 on day 21. Morphometry (GSI and TII) revealed that renal lesions were more progressive in group 2 than in group 1. Glomeruli in group 2 were markedly larger than those in group 1, but no difference in glomerular volume was noted between groups 1 and 3.
Our findings suggest that CCB prevent progression of renal injury induced by accelerated hypertension in UNX SHR. the mechanisms of prevention may, at least in part, be related to suppression of glomerular hypertrophy. Inhibition of renal injury can be achieved without significant reduction of proteinuria.     

Histological grading of IgA nephropathy predicting renal outcome: revisiting H. S. Lee's glomerular grading system.

BACKGROUND: The glomerular grading system is useful to compare biopsy specimens and to predict the natural course of disease in IgA nephropathy (IgAN), although no grading system can be perfect. METHODS: H. S. Lee's grading system for IgAN was refined as follows: grade I, normal or focal mesangial cell proliferation; grade II, diffuse mesangial cell proliferation, or <25% of glomeruli with crescent (Cr)/segmental sclerosis (SS)/global sclerosis (GS); grade III, 25-49% of glomeruli with Cr/SS/GS; grade IV, 50-75% of glomeruli with Cr/SS/GS; grade V, >75% of glomeruli with Cr/SS/GS. This refined H. S. Lee grading system was then tested for clinical relevance on 187 patients with IgAN followed up for an average of 6.5 years (minimum, 3 years). In the survival analysis, a modified primary end-point (progressive renal disease) was used. RESULTS: The glomerular grades were significantly related to hypertension, serum creatinine levels and the amounts of proteinuria at time of biopsy. By univariate analysis, glomerular grades, hypertension, renal insufficiency and significant proteinuria (> or =1 g/day) were significantly associated with progressive renal disease. By multivariate analysis using the Cox regression model, glomerular grades, renal insufficiency and significant proteinuria were independent prognostic factors for progressive renal disease. At the end of follow-up, glomerular grades were significantly related to serum creatinine levels, amounts of proteinuria, hypertension and progressive renal disease. CONCLUSIONS: These findings indicate that the refined H. S. Lee grading system for IgAN is useful in assessing the patients' clinical outcome and is sufficiently simple and easy to reproduce as to be universally applicable in prognostic work.     

Angiotensin-converting enzyme insertion/deletion polymorphism and prognosis of IgA nephropathy

BACKGROUND/AIM: Well-known factors for a poor prognosis in IgA nephropathy (IgAN) are hypertension, proteinuria, and renal insufficiency at the time of diagnosis. Also hypertriglyceridemia and hyperuricemia seem to play a role in the progression of IgAN. Angiotensin-converting enzyme (ACE) gene I/D polymorphism has been associated with cardiovascular diseases and with progression of IgAN. We, therefore, investigated the contribution of ACE gene I/D polymorphism in the prognosis of IgAN and its association with the other risk factors affecting the prognosis. METHODS: A total of 168 patients with IgAN were followed up for 6-17 (median 11) years from renal biopsy with respect to progression of renal disease defined as elevation of serum creatinine above 125 microM (1.4 mg/dl) in men or 105 microM (1.2 mg/dl) in women and over 20% from the baseline level. In addition to serum creatinine, the urinary protein excretion was evaluated at the time of renal biopsy and at the assessment visit at the end of the follow-up period. RESULTS: During the follow-up period, 26 (15%) patients showed progression of renal disease. Patients with ACE genotype II had a more favorable course than those with genotypes ID or DD. Although there were no significant differences among the ACE genotypes with respect to proteinuria > or =1 g/24 h at the time of renal biopsy, proteinuria > or =1 g/24 h was more frequent in patients with genotypes ID or DD than in those with genotype II at the end of the follow-up period. No associations were found between hypertension, serum lipids or serum urate, and ACE genotypes. CONCLUSIONS: Our results show that patients with ACE genotype II have a more favorable prognosis than those with genotypes ID/DD. Secondly, proteinuria (> or =1 g/24 h) found in patients with genotype II at diagnosis may improve, while in patients with genotypes ID/DD it is a more constant feature.     

Primary focal sclerosing glomerulonephritis: A clinicopathological analysis

SUMMARY: The clinical and laboratory features, renal biopsy findings, and outcome of 68 patients with primary focal sclerosing glomerulonephritis were studied. the cumulative probability of not progressing to end-stage renal failure (ESRF) was 0.92 at 5 years and 0.73 at 10 years after presentation, and was significantly worse in patients with hypertension or severe renal impairment (serum creatinine >0.24 mmol/L) at presentation. Proteinuria of up to 1gm/day was associated with an excellent prognosis, whereas proteinuria of 1–3 gm/day and >3 gm/day had similar and poorer survivals. an adverse outcome was associated with, at presentation, age less than 30 years, hypertension, a family history of glomerulonephritis, cigarette smoking, impaired renal function, and heavy proteinuria. Renal biopsy findings which correlated with progressive renal failure included a higher percentage of glomeruli with global or segmental sclerosis, and the degrees of tubular atrophy, interstitial fibrosis, interstitial inflammation and arterial thickening. During follow-up the degrees of renal impairment and proteinuria, persistence or development of hypertension, transient decreases of renal function of >10%, and the total number of red cells and casts on centrifuged urine microscopy were all predictive of progressive renal disease. Multivariate analysis demonstrated that the indices with adverse effects on outcome induced all of the above except tubulointerstitial and vascular changes on renal biopsy. It is concluded that the prognosis may be better than has been suggested in the literature. It is possible to predict which patients are likely to have an adverse outcome, and this should assist with therapeutic decisions likely to retard progression of disease.     

The ratio of epidermal growth factor to monocyte chemotactic peptide-1 in the urine predicts renal prognosis in IgA nephropathy

The production of cytokines by resident and non-resident renal cells during immunoglobulin A nephropathy (IgAN) plays a key role in the progression of renal damage. The aim of this study was to determine if measurements of urinary epidermal growth factor (EGF) and monocyte chemotactic peptide-1 (MCP-1), at the time of renal biopsy, were a predictor of end-stage renal disease (ESRD) in a cohort of 132 patients with biopsy-proven IgAN. Outcome measures were a doubling of the baseline serum creatinine (sCr) and/or ESRD. Patients with ratios of EGF/MCP-1 in the lowest tertile had a significant decline in renal survival, while patients in the highest tertile maintained 100% renal survival at 48 and 84 months of follow-up. Multivariate Cox's regression analysis showed that the urine EGF/MCP-1 ratio was an independent prognostic factor and indirectly correlated with the combined outcome. The predictive value was also measured by the area under the receiver operating characteristic curve (ROC). The area of the EGF/MCP-1 ratio was significantly higher than that of EGF or MCP-1 alone, histologic grade, creatinine clearance, or proteinuria. Our study suggests that the urinary EGF/MCP-1 ratio may be used as a prognostic marker of ESRD for patients with IgAN.     

Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome

Among the numerous studies published in the last 20 years that have calculated the actuarial renal survival and tried to individuate the prognostic role of the clinical and histologic features present at the onset of the disease or the time of biopsy, we chose to critically analyze the results of the most valid (23 studies). Actuarial renal survival at 10 years in adults was between 80% and 85% in most of the European, Asian, and Australian studies, but was lower than this in studies from the United States and exceeded 90% in the few studies on children. Concordance existed in this selected literature on the fact that impairment of renal function, severe proteinuria, and arterial hypertension are the strongest and more reliable clinical predictors of an unfavorable outcome. Extent of proteinuria during follow up was an even stronger predictor. In adult patients, a high score of the glomerular and tubulointerstitial lesions predicted a more rapid progression. When the single lesions were analyzed separately, glomerular sclerosis and interstitial fibrosis appeared to be the strongest, most reliable predictors of unfavorable prognosis. More controversial was the role of crescents and capsular adhesions.     

GMP-17-positive T-lymphocytes in renal tubules predict progression in early stages of IgA nephropathy

Treatment of patients with IgA nephropathy (IgAN) depends on a reliable assessment of disease progression based on measurements of glomerular filtration rate (GFR), proteinuria, hypertension, and tubulointerstitial changes. We sought to determine whether progression could be predicted from analysis of glomerular and tubulointerstitial inflammation in biopsies taken at an early stage of IgAN. We retrospectively analyzed biopsies from 50 patients, relating the subsequent clinical course to infiltration with B- and T-lymphocytes, granule membrane protein of 17 kDa (GMP-17) positive cytotoxic T cells, macrophages, fibroblasts, and tubulointerstitial expression of human leukocyte antigen-D related (HLA-DR). At biopsy, 19 patients had decreased GFR while 13 of 31 patients with normal GFR and progressive IgAN differed significantly from 18 non-progressors in the level of proteinuria and in the severity of scores for mesangial proliferation, tubular atrophy, interstitial fibrosis, and interstitial infiltrates. On multivariate regression analysis these differences disappeared; however, associations with GMP-17-positive cytotoxic T-lymphocytes in intact renal tubules and of B-lymphocytes in the interstitium remained significant. Our study may have identified a marker of disease progression in early stages of IgAN.     

Tubulointerstitial nephritis and uveitis (TINU) syndrome in a 52-year-old female: a case report and review of the literature

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare entity first described in 1975, affecting mainly young women and adolescents. We present a case of a 52-year-old female patient (one of the oldest in the literature) who complained of fever, anorexia, nausea, and vomiting. After she was admitted to our hospital, laboratory tests revealed tubular proteinuria, elevated erythrocyte sedimentation rate (ESR), anemia, and renal insufficiency (serum creatinine 4.2 mg/dL) with metabolic acidosis. Ophthalmologic examination revealed anterior uveitis (iritis) and renal biopsy showed acute tubulointerstitial nephritis. The diagnosis of TINU syndrome was established and the patient was treated with oral corticosteroids. All symptoms and ophthalmologic abnormalities disappeared after 6 weeks of treatment. Renal function also recovered completely and remained stable at follow-up. TINU syndrome should be considered in the differential diagnosis of unexplained tubulointerstitial nephritis, especially in the presence of ocular findings. Corticosteroid therapy is still controversial, but it helps in the quick resolution of renal and mainly eye abnormalities.     

Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome in a 52-Year-Old Female: A Case Report and Review of the Literature

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare entity first described in 1975, affecting mainly young women and adolescents. We present a case of a 52-year-old female patient (one of the oldest in the literature) who complained of fever, anorexia, nausea, and vomiting. After she was admitted to our hospital, laboratory tests revealed tubular proteinuria, elevated erythrocyte sedimentation rate (ESR), anemia, and renal insufficiency (serum creatinine 4.2 mg/dL) with metabolic acidosis. Ophthalmologic examination revealed anterior uveitis (iritis) and renal biopsy showed acute tubulointerstitial nephritis. The diagnosis of TINU syndrome was established and the patient was treated with oral corticosteroids. All symptoms and ophthalmologic abnormalities disappeared after 6 weeks of treatment. Renal function also recovered completely and remained stable at follow-up. TINU syndrome should be considered in the differential diagnosis of unexplained tubulointerstitial nephritis, especially in the presence of ocular findings. Corticosteroid therapy is still controversial, but it helps in the quick resolution of renal and mainly eye abnormalities.     

Primary focal sclerosing glomerulonephritis: A clinicopathological analysis

The clinical and laboratory features, renal biopsy findings, and outcome of 68 patients with primary focal sclerosing glomerulonephritis were studied. The cumulative probability of not progressing to end-stage renal failure (ESRF) was 0.92 at 5 years and 0.73 at 10 years after presentation, and was significantly worse in patients with hypertension or severe renal impairment (serum creatinine >0.24 mmol/L) at presentation. Proteinuria of up to 1gm/day was associated with an excellent prognosis, whereas proteinuria of 1–3 gm/day and >3 gm/day had similar and poorer survivals. An adverse outcome was associated with, at presentation, age less than 30 years, hypertension, a family history of glomerulonephritis, cigarette smoking, impaired renal function, and heavy proteinuria. Renal biopsy findings which correlated with progressive renal failure included a higher percentage of glomeruli with global or segmental sclerosis, and the degrees of tubular atrophy, interstitial fibrosis, interstitial inflammation and arterial thickening. During follow-up the degrees of renal impairment and proteinuria, persistence or development of hypertension, transient decreases of renal function of >10%, and the total number of red cells and casts on centrifuged urine microscopy were all predictive of progressive renal disease. Multivariate analysis demonstrated that the indices with adverse effects on outcome included all of the above except tubulointerstitial and vascular changes on renal biopsy. It is concluded that the prognosis may be better than has been suggested in the literature. It is possible to predict which patients are likely to have an adverse outcome, and this should assist with therapeutic decisions likely to retard progression of disease.     

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.     

Recurrence of IgA nephropathy 17 months after renal transplantation in the allograft transmitted thin basement membrane disease (TBMD) from donor

Recurrence of IgA nephropathy (IgAN) following renal transplantation has been described in 40-50% of such patients and it usually has a good outcome. We present the case of a 20-yr-old woman with IgAN who developed end-stage renal failure in 1995. In November 1996, she received a kidney from a living-related donor and was treated with tacrolimus, azathioprine and steroids. Zero- and one-hour biopsies were performed, which revealed minor glomerular abnormalities in light microscopy, thin basement membrane disease (TBMD) in electron microscopy. Eight months later she developed microscopic hematuria and proteinuria; however, the graft function was normal. Renal biopsy revealed an IgAN that is thought to be due to recurrence of the original disease.