The natural history of IgA nephritis in Singapore

The clinical and histological features of 151 patient with IgA nephritis were analyzed to determine the prognostic features of the disease. The mean duration of follow up examinations was 50 +/- 34 months (range 6 to 168 months). The majority of the patients were young males and showed no signs of IgA nephritis. The disease was detected by routine screening before induction into national service. The plot of the reciprocals of serum creatinine against time in the patients with progressive disease showed that the patients ran two different courses when they developed renal impairment; one was a slow progressive course over an average of 7.7 years before reaching end stage renal failure (ESRF), while the other was a more rapid decline to ESRF within an average of 3.3 years in which severe uncontrolled hypertension seemed to be the major adverse factor. Hypertension was present in 23% of patients. Nine percent had renal impairment at the end of the follow up period while 5% progressed to ESRF. The cumulative renal survival was 91% after 6 years with no further development of renal failure up to 14 years. Unfavorable long term prognostic indices were proteinuria of more than 2 gm, hypertension and presence of crescents on renal biopsy.     

The natural history of untreated "prostatism"

One hundred and seven patients with symptoms of prostatic obstruction in whom prostatectomy was not clinically indicated were reviewed after an interval of 5 years. Ten had subsequently required surgery and 97 remained untreated. In the majority, symptoms did not worsen and only 2 developed acute retention. Urodynamic studies, where repeated, showed little change. Although there was no certain indicator or progression, a flow rate measurement could identify the patients at risk of clinical deterioration sufficient to require surgery.     

Clinical features and natural history in adults with IgA nephropathy

Two different clinical syndromes might be observed at presentation in most patients with IgA nephropathy (IgAN): (1) an acute reversible episode of macroscopic hematuria or (2) asymptomatic urinary abnormalities. Patients in these groups differ by genetic markers, the severity of their histologic lesions, and the rate of progression to renal insufficiency. Macroscopic hematuria is more common in children, and its frequency decreases with increasing age. In our experience, most patients presenting in adulthood with macroscopic hematuria did not have proteinuria or microscopic hematuria prior to the episode of macroscopic hematuria, suggesting the onset of disease was indeed in adulthood. IgAN is not a benign disease. About 20% of patients reach end-stage renal failure after 20 years of clinical disease. Features generally associated with a poor prognosis include older age at onset, no history of recurrent macroscopic hematuria, hypertension, and consistent proteinuria. In some studies, men progressed more rapidly than women. Using the regression of Cox in the present study, the magnitude of proteinuria was the only clinical parameter that independently predicted progressive renal impairment.     

"Point of no return (PNR)" in progressive IgA nephropathy: significance of blood pressure and proteinuria management up to PNR

BACKGROUND: Based on observations of the clinical course in patients with IgA nephropathy (IgAN), D'Amico et al proposed the concept of the "point of no return (PNR)", after which progression to end-stage renal disease (ESRD) becomes inevitable. They reported that the approximate PNR is serum creatinine (sCr) 3.0 mg/dL. METHODS: To confirm the PNR and to clarify the factors affecting renal function deterioration in IgAN patients, we analyzed the sequential data of those with 1.2 or= 102 mmHg and/or urinary protein (UP) score >or= 2.0 with sCr up to 2.0 mg/dL was significantly poor. Multivariate analysis using the Cox's proportional hazards model, identified only MBP and UP during the course until sCr reached 2.0 mg/dl as independent prognostic factors for ESRD, having hazard ratios of 2.56 (per 10 mmHg; 95% confidence interval (95% CI) 1.08-6.05) and 4.37 (per 0.5 point; 95% CI 1.36-14.1), respectively. CONCLUSIONS: We confirmed PNR as a sCr level of 2.0 mg/dL (equivalent to estimated glomerular filtration rate (GFR) of 30-35 mL/min/1.73m2) during the course of IgAN in Japan. Proper management of both BP and UP until sCr has reached PNR is essential to arrest the progression to ESRD in IgAN.     

Treatment of IgA nephritis in Singapore

Summary: Any form of therapy for IgA nephritis must be rational and practical. the least toxic agent should be chosen with a view to even life long therapy for patients with bad prognostic indices. Patients with IgA nephritis have evidence of platelet involvement and low-grade intravascular coagulation, with a tendency for increased thrombogenicity within the kidneys. the use of dipyridamole (an anti-platelet agent) and warfarin (an anti-thrombotic agent) has been successful in two separate trials in patients with IgA nephritis. the relative lack of side-effects and their low cost allow their long-term use for treatment in these patients. the indications for combination therapy with dipyridamole and low dose warfarin are the presence of any one of the following parameters: proteinuria < 1 g m/day, hypertension, renal impairment, glomerulosclerosis < 20% on renal biopsy, presence of even a single crescent, medial hyperplasia of blood vessels on biopsy. Treatment of patients with IgA nephritis with asymptomatic haematuria and proteinuria consist of control of systemic hypertension, use of ACE inhibitor for glomerular hyperfiltration, dipyridamole and low dose warfarin, low protein diet (0.8 g/kg per body weight/day) and control of serum cholesterol to prevent lipid induced glomerulosclerosis. Patients with IgA nephritis who have the nephrotic syndrome with selective proteinuria, should be treated with prednisolone. Those who do not respond to steroids can be given a course of cyclophosphamide. Patients with IgA nephritis with predominantly tubular interstitital lesions not in proportion to the degree of glomerular sclerosis should be treated with a low dose steroid regimen. While there is no cure for IgA nephritis such therapeutic measures serve to retard the progression to end-stage renal failure (ESRF). Future therapeutic strategies lie in immunomodulation using inhibitors of cytokines and possibly gene therapy.     

The natural history of coronary calcification progression in a cohort of nocturnal haemodialysis patients.

BACKGROUND: End-stage renal disease (ESRD) is associated with a markedly increased cardiac calcification burden, as reflected by computed tomography scans of the heart. Nocturnal haemodialysis (NHD) is a novel form of renal replacement therapy which has multiple physiologic effects that may affect vascular calcification, including improvements in phosphate and uraemia control. The objective of the present study is the determination of the natural history of coronary calcification progression in patients converted to NHD, and the examination of the relationships between calcification risk factors and calcification progression in these patients. METHODS: Thirty-eight ESRD patients were converted to NHD, and included in our observational cohort study. Coronary artery calcification scores (CACS) were documented at baseline and post-conversion (mean interscan duration 16+/-1 months). Other variables of interest included age, dialysis vintage, Framingham risk profile, phosphate binder and vitamin D usage, and plasma levels of calcium, phosphate and parathyroid hormone. RESULTS: Our cohort was stratified according to baseline calcification burden (minimal calcification: CACS < or = 10 vs significant calcification: CACS > 10). Twenty-four patients had baseline CACS < or = 10. These patients demonstrated no change in coronary calcification after 1 year of NHD (from 0.7+/-0.5 to 6+/-3, P = 0.1). Fourteen patients had higher initial CACS at baseline (1874+/-696), and demonstrated a non-significant 9% increase over 1 year to 2038+/-740 (P = 0.1). Plasma phosphate and calcium x phosphate product were significantly reduced, as were calcium-based phosphate binder and antihypertensive usage. CONCLUSIONS: Our study is the first to document CACS progression in a cohort of NHD patients. Further analysis of the effect of NHD on the physiology of cardiovascular calcification is required.     

Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy

IgA nephropathy is one of the most common causes of glomerulonephritis in the world and is characterized histologically by the deposition of polymeric forms of IgA within the mesangium and in some cases along the glomerular capillary wall.(1) Proliferative and crescenteric forms of IgA are associated with nephrotic range proteinuria, accelerated hypertension, and a more rapid decline toward end-stage renal disease. Previous attempts to categorize the incidence and clinical significance of proliferative IgA nephropathy have given conflicting results. This is in part the result of the lack of a uniform nomenclature and the failure of clinical therapies to prolong renal survival in specific subgroups. In the present study, we performed a prospective open-label trial of pulse solumedrol and intravenous cyclophosphamide in 20 patients with IgA nephropathy and at least 10% cellular crescents or endocapillary proliferation on renal biopsy. Seventeen patients underwent repeat kidney biopsies after 6 months of therapy, and the morphologic response to treatment was assessed using a modified systemic lupus erythematosis (SLE) histologic activity and chronicity index score. To determine the long-term efficacy of intravenous cyclophosphamide on renal survival, the results of the treated patients were compared with 12 untreated historical controls. Pulse solumedrol and intravenous cyclophosphamide effectively reduced peak serum creatinine, degree of proteinuria, the rate of decline in renal function, and the incidence of end-stage renal disease at 36 months.     

Monocyte infiltration and cross-linked fibrin deposition in IgA nephritis and Henoch-Schoenlein purpura nephritis

To clarify the role of immune cell infiltration and fibrin deposition in glomerular injury, renal biopsy specimens taken from patients with primary IgA nephritis and Henoch-Sch?nlein purpura nephritis (HSPN) were evaluated using monoclonal antibodies specific to mononuclear cell surfaces and cross-linked fibrin (XFb). Monocytes/macrophages were the predominant cell type infiltrating glomeruli in IgA nephritis and HSPN. The intraglomerular monocyte population in both diseases was significantly higher than that in normals, mesangial proliferative (non-IgA) glomerulonephritis or minimal change nephrotic syndrome. In IgA nephritis, there was a clear correlation between glomerular monocyte accumulation and the degree of proteinuria. Although the monocyte influx tended to decline with time in HSPN, it remained unchanged in IgA nephritis. XFb deposition was found in the glomeruli of 27 out of 48 patients with IgA nephritis, and in 15 out of 20 with HSPN. The degree of XFb deposition in IgA nephritis correlated significantly with the degree of mesangial proliferation. These findings indicate a close relationship of monocyte/macrophage infiltration and XFb deposition with glomerular injury in IgA nephritis.     

Age-related character of glomerular lesions in IgA nephritis

In relation to the phenomenon in which IgA nephritis is carried over from childhood to an adult age, pathohistological analysis was performed to elucidate the age-related character of the expression of the disease based on renal biopsy specimens from different age groups. A significant difference in the glomerular lesions was noted between the age groups under 15 yrs (15 +/- 2.1 yrs) and over 18 yrs. In the younger age group, the disease became manifest with lesser glomerular sclerosis and segmental lesions, whereas mesangial proliferative and sclerosing lesions were evident with increasing segmental lesions in the adult-onset disease. It is suggested that some of the childhood cases of IgA nephritis with progressive mesangial sclerosis could be carried over to an adult age.     

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.     

Microvascular disease and the progression of IgA nephropathy

In order to examine the role of microvascular disease in the evolution of IgA nephropathy (IgAN), the interrelationships among vascular sclerosis, glomerular sclerosis, age, and hypertension were determined by morphometric analysis of renal biopsies in 71 patients with IgAN; 63 age- and sex-matched individuals with minimal change nephrotic syndrome (MCNS) served as normal controls. The following parameters in glomeruli and in vessels with an outer diameter of 60 microns or less were analyzed by multiple regression analysis: (1) percentage of glomeruli with segmental and/or global sclerosis; (2) percentage of vessel area in renal cortical tissue measured by the point-counting method; (3) index of hyaline change estimated as the percentage of the number of arteries showing hyaline change; (4) index of vessel wall thickness determined by the ratio of mural thickness to outer diameter of arteries; (5) number of vascular cross sections counted per 6.25 microns2. The results of the multiple regression analysis demonstrate that glomerular and vascular sclerosis are interrelated and that hypertension and vessel area are almost equally important as predictors of glomerular sclerosis. Vessel area proved to be an early marker of vasculopathy, as its values in IgAN, even in the absence of hypertension and/or glomerular sclerosis, exceeded those in age- and sex-matched controls (with MCNS). These data, obtained by the use of quantitative methods, establish a role for vessel disease and hypertension in the progression of IgAN.     

Hyperuricemia aggravates the progression of IgA nephropathy

International Urology and Nephrology - The relationship between hyperuricemia and IgA nephropathy (IgAN) was evaluated systematically in this research. The Preferred Reporting Items for Systematic...