Current guidelines suggest treatment with corticosteroids (CS) in IgA nephropathy (IgAN) when proteinuria is persistently ≥1 g/d despite 3-6 months of supportive care and when eGFR is >50 ml/min per ...1.73 m(2). Whether the benefits of this treatment extend to patients with an eGFR≤50 ml/min per 1.73 m(2), other levels of proteinuria, or different renal pathologic lesions remains unknown. We retrospectively studied 1147 patients with IgAN from the European Validation Study of the Oxford Classification of IgAN (VALIGA) cohort classified according to the Oxford-MEST classification and medication used, with details of duration but not dosing. Overall, 46% of patients received immunosuppression, of which 98% received CS. Treated individuals presented with greater clinical and pathologic risk factors of progression. They also received more antihypertensive medication, and a greater proportion received renin angiotensin system blockade (RASB) compared with individuals without immunosuppressive therapy. Immunosuppression was associated with a significant reduction in proteinuria, a slower rate of renal function decline, and greater renal survival. Using a propensity score, we matched 184 subjects who received CS and RASB to 184 patients with a similar risk profile of progression who received only RASB. Within this group, CS reduced proteinuria and the rate of renal function decline and increased renal survival. These benefits extended to those with an eGFR≤50 ml/min per 1.73 m(2), and the benefits increased proportionally with the level of proteinuria. Thus, CS reduced the risk of progression regardless of initial eGFR and in direct proportion to the extent of proteinuria in this cohort.
Treatment of IgA nephropathy Barratt, J.; Feehally, J.
Kidney international,
06/2006, Letnik:
69, Številka:
11
Journal Article
Recenzirano
Odprti dostop
IgA nephropathy (IgAN) is an important cause of progressive kidney disease with 25–30% of patients developing end-stage renal disease within 20 years of diagnosis. There is still no treatment to ...modify mesangial IgA deposition and available treatments are those extrapolated from the management of other patterns of chronic glomerulonephritis. There remains no consensus on the use of immunosuppressive agents for treatment of progressive IgAN and this is compounded by the relative lack in IgAN of randomized controlled trials relevant to current clinical practice. Patients with recurrent macroscopic hematuria or isolated microscopic hematuria and proteinuria <1 g/24 h require no specific treatment. Those with nephrotic syndrome and minimal change on renal biopsy should be managed as for minimal change nephropathy. There is no evidence to support the use of corticosteroids for nephrotic IgAN outside this group of patients. Patients presenting with acute renal failure require evaluation to distinguish acute tubular necrosis, which requires supportive therapy only, from crescentic IgAN, for which treatment with cyclophosphamide and corticosteroids in a regimen similar to that for renal small vessel vasculitis is indicated in the absence of significant chronic histologic injury. Patients at greatest risk of progressive renal impairment are those with hypertension, proteinuria >1 g/24 h, and reduced glomerular filtration rate at diagnosis. All such patients should be treated to a blood pressure of 125/75 mm Hg with dual blockade of the renin–angiotensin system with angiotensin-converting enzyme inhibition and angiotensin receptor blockade. At present, there is insufficient evidence for the additional use of immunosuppressive agents, antiplatelet agents, or anticoagulants.
There is increasing evidence of the benefit of regular physical exercise in a number of long-term conditions including chronic kidney disease (CKD). In CKD, this evidence has mostly come from studies ...in end stage patients receiving regular dialysis. There is little evidence in pre-dialysis patients with CKD Stages 4 and 5.
A prospective study compared the benefits of 6 months regular walking in 40 pre-dialysis patients with CKD Stages 4 and 5. Twenty of them were the exercising group and were compared to 20 patients who were continuing with usual physical activity. In addition, the 40 patients were randomized to receive additional oral sodium bicarbonate (target venous bicarbonate 29 mmol/L) or continue with previous sodium bicarbonate treatment (target 24 mmol/L).
Improvements noted after 1 month were sustained to 6 months in the 18 of 20 who completed the exercise study. These included improvements in exercise tolerance (reduced exertion to achieve the same activity), weight loss, improved cardiovascular reactivity, avoiding an increase in blood pressure medication and improvements in quality of health and life and uraemic symptom scores assessed by questionnaire. Sodium bicarbonate supplementation did not produce any significant alterations.
This study provides further support for the broad benefits of aerobic physical exercise in CKD. More studies are needed to understand the mechanisms of these benefits, to study whether resistance exercise will add to the benefit and to evaluate strategies to promote sustained lifestyle changes, that could ensure continued increase in habitual daily physical activity levels.
Patients with advanced chronic kidney disease (CKD), especially those on long-term dialysis, often suffer from muscle wasting and excessive fatigue. It is known that inactivity, muscle wasting and ...reduced physical functioning are associated with increased mortality in CKD. Known causes include uraemic myopathy and neuropathy, inactivity, and anaemia. Exercise in patients receiving regular dialysis treatment for end-stage renal disease was first introduced 3 decades ago, but is still only offered in a minority of renal units around the world, despite a significant body of evidence to support its use. Work is needed to increase awareness of the potential benefits of increased physical activity for patients with advanced CKD. This review summarizes the mechanisms of exercise intolerance and debility in advanced CKD patients, the methods used for the estimation of functional capacity, the options currently available for exercise training, and their influence on the well-being of this group of patients.
In IgA nephropathy (IgAN), pathogenic IgA1 is likely derived from bone marrow (BM) cells and exhibits reduced O-galactosylation. Defective O-galactosylation may arise from the compromised expression ...or function of the enzyme β-galactosyltransferase and/or its molecular chaperone (Cosmc). We measured B-cell O-galactosylation activity and the relative gene expression of β-galactosyltransferase and Cosmc in peripheral blood and BM taken from patients with IgAN and controls. O-galactosylation activity was measured in peripheral and BM B cells by the incorporation of radiolabeled galactose into an asialo-mucin acceptor. Gene expression of β-galactosyltransferase and Cosmc was measured by real-time PCR and related to that of the enzyme GalNAc-T2 (UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-2), which synthesizes the core O-glycan. Neither the B-cell O-galactosylation activity nor the gene expression of the enzyme or chaperone was different between patients and controls. However, the relationships between the O-glycosylation of serum IgA1, galactosylation activity, and β-galactosyltransferase gene expression showed different patterns in IgAN and controls. In IgAN, O-galactosylation activity correlated with β-galactosyltransferase gene expression, but not with IgA1 O-glycosylation, suggesting that factors other than the availability of β-galactosyltransferase or Cosmc are responsible for altered IgA1 O-glycosylation.
On April 7–8, 2014, the European Hydration Institute hosted a small group of experts at Castle Combe Manor House, United Kingdom, to discuss a range of issues related to human hydration, health, and ...performance. The meeting included 18 recognized experts who brought a wealth of experience and knowledge to the topics under review. Eight selected topics were addressed, with the key issues being briefly presented before an in-depth discussion. Presented here is the executive summary and conclusions from this meeting.
The International Society of Nephrology’s (ISN) 0by25 initiative aims to prevent avoidable deaths from acute kidney injury (AKI) by 2025, most of which occur in low and lower middle-income countries ...(LLMICs). To increase evidence about the epidemiology of AKI, especially in LLMICs, ISN conducted a ‘Global Snapshot’, a multinational, cross-sectional study in which 322 physicians from 72 countries in 6 continents identified 3,664 adults and 354 children with AKI who were under their care of which 45% were from LLMICs, nevertheless lowincome countries were under-represented. In LLMICs, patients with AKI were younger, and community acquired AKI was more common. Hypotension (40%) and dehydration (39%) were the most common causes of AKI. Dehydration was a more common cause in LLMIC, as were sepsis, pregnancy-related AKI and animal envenomation. Acute dialysis was performed in 23% of patients. Eight percent had a clinical indication for this but were not dialyzed. In LLMICs, lack of resources (16%) and inability to afford therapy (30%) accounted for almost half of these cases. Overall mortality at 7 days was 11% and was higher in LLMICs. Complete recovery from AKI occurred in 30% of patients and partial recovery 37%, and was more often complete in LLMICs. The 0by25 Global Snapshot provides new information about the worldwide epidemiology of AKI, helping to identify elements that would be amenable in intervention to reduce preventable deaths.
Chronic Kidney Disease (CKD) is a long-term progressive condition affecting 10-15% of people. The overlap of diabetes, hypertension and CKD in an aging population means that prevalence will only ...increase. CKD increases the risk of all-cause mortality, secondary to the elevated cardiovascular risk. It also significantly affects the patients' ability to engage in functional activities and their quality of life. The evidence base suggests that exercise has the capacity to improve symptom burden, functional ability and mental health. The majority of the patient population are pre-dialysis yet previous research has concentrated on dialysing patients. This review will focus on the patient group not requiring renal replacement therapy (non-RRT) as this is an area where further work is urgently needed. A large majority of people with CKD tend to be inactive despite emerging guidelines emphasising the positive effect of exercise for both people with chronic disease and healthy populations. This paper will review the evidence to support exercise to improve outcomes and quality of life and report on common barriers that patients experience and advocate the need for supported exercise interventions to help patients become more active and gain the potential resultant health benefits.
Background. ‘Seronegative lupus nephritis’ describes patients with renal histology typical of lupus nephritis who have no clinical or serological evidence of systemic lupus erythematosus (SLE). We ...report our experience in nine patients identified as having ‘seronegative lupus nephritis’ who met the diagnostic criteria for C1q nephropathy. Methods. A retrospective review of clinical case notes and renal histology was carried out. Results. We describe nine patients with C1q nephropathy in whom the diagnosis of ‘seronegative lupus nephritis’ was initially considered. All had renal histological features typical of lupus nephritis with ‘wire loop’ appearances on light microscopy, ‘full house’ immunoglobulin and complement deposition by immunoperoxidase, and electron-dense deposits in at least two glomerular locations. None of these nine patients developed clinical or serological evidence of SLE over a median follow-up of 6 years (range 0.1–9). There was no consistent evidence of a response to immunosuppressive therapy. In all cases, C1q staining was dominant on immunoperoxidase, and no tubuloreticular inclusions were seen. These appearances accord with previous descriptions of C1q nephropathy. Conclusions. The implications of a diagnosis of lupus are considerable, and we propose that the term ‘seronegative lupus nephritis’ is unhelpful, and should be avoided when there is diagnostic uncertainty. The term C1q nephropathy should be preferred when these histological features are seen in the absence of overt lupus, when C1q deposition is dominant and when tubuloreticular bodies are absent. The clinical course in the cases reported here does not support the use of immunosuppressive therapy in C1q nephropathy.
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