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Renal AND Proteinuria [keywords]
- Patient Age and the Prognosis of Idiopathic Membranous Nephropathy. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110376.
Idiopathic membranous nephropathy (IMN) is increasingly seen in older patients. However, differences in disease presentation and outcomes between older and younger IMN patients remain controversial. We compared patient characteristics between younger and older IMN patients.We recruited 171 Japanese patients with IMN, including 90 (52.6%) patients <65 years old, 40 (23.4%) patients 65-70 years, and 41 (24.0%) patients ≥71 years. Clinical characteristics and outcomes were compared between younger and older IMN patients.During a median observation period of 37 months, 103 (60.2%) patients achieved complete proteinuria remission, which was not significantly associated with patient age (P = 0.831). However, 13 (7.6%) patients were hospitalized because of infection. Multivariate Cox proportional hazards models identified older age [adjusted hazard ratio (HR) = 3.11, 95% confidence interval (CI): 1.45-7.49, per 10 years; P = 0.003], prednisolone use (adjusted HR = 11.8, 95% CI: 1.59-242.5; P = 0.014), and cyclosporine used in combination with prednisolone (adjusted HR = 10.3, 95% CI: 1.59-204.4; P = 0.012) as significant predictors of infection. A <25% decrease in proteinuria at 1 month after immunosuppressive therapy initiation also predicted infection (adjusted HR = 6.72, 95% CI: 1.51-37.8; P = 0.012).Younger and older IMN patients had similar renal outcomes. However, older patients were more likely to develop infection when using immunosuppressants. Patients with a poor response in the first month following the initiation of immunosuppressive therapy should be carefully monitored for infection and may require a faster prednisolone taper.
- Effects of T-Type Calcium Channel Blockers on Renal Function and Aldosterone in Patients with Hypertension: A Systematic Review and Meta-Analysis. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e109834.
High blood pressure can cause kidney damage, which can increase blood pressure, leading to a vicious cycle. It is not clear whether the protective effects of T-type calcium channel blockers (T-type CCBs) on renal function are better than those of L-type CCBs or renin-angiotensin system (RAS) antagonists in patients with hypertension.PUBMED, MEDLINE, EMBASE, OVID, Web of Science, Cochrane, CNKI, MEDCH, VIP, and WANFANG databases were searched for clinical trials published in English or Chinese from January 1, 1990, to December 31, 2013. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated and reported. A total of 1494 reports were collected, of which 24 studies with 1,696 participants (including 809 reports comparing T-type CCBs versus L-type CCBs and 887 reports comparing T-type CCB versus RAS antagonists) met the inclusion criteria. Compared with L-type CCBs, T-type CCBs resulted in a significant decline in aldosterone (mean difference = -15.19, 95% CI -19.65--10.72, p<1×10-5), proteinuria (mean difference = -0.73, 95% CI -0.88--0.57, p<1×10-5), protein to creatinine ratio (mean difference = -0.22, 95% CI -0.41--0.03, p = 0.02), and urinary albumin to creatinine ratio (mean difference = -55.38, 95% CI -86.67--24.09, p = 0.0005); no significant difference was noted for systolic blood pressure (SBP) (p = 0.76) and diastolic blood pressure (DBP) (p = 0.16). The effects of T-type CCBs did not significantly differ from those of RAS antagonists for SBP (p = 0.98), DBP (p = 0.86), glomerular filtration rate (p = 0.93), albuminuria (p = 0.97), creatinine clearance rate (p = 0.24), and serum creatinine (p = 0.27) in patients with hypertension.In a pooled analysis of data from 24 studies measuring the effects of T-type CCBs on renal function and aldosterone, the protective effects of T-type CCBs on renal function were enhanced compared with L-type CCBs but did not differ from RAS antagonists. Their protective effects on renal function were independent of blood pressure.
- Teenager male with burning pain in extremities--suspect Fabry disease, 2 case reports. [Journal Article]
- J Assoc Physicians India 2014 Jan; 62(1):69-71.
We present 2 cases of teenager males presented with burning pain in extremities and turned out to be cases of Fabry disease.The purpose of presenting this case is to highlight the fact that suspicion of Fabry disease in patients presenting with these symptoms will lead to early diagnosis and treatment of this condition before occurrences of complications.A 14-year-old male presented with severe burning pain in both hands and feet since last 4 yrs which persisted despite consumption of painkillers and becoming more disabling and without having any family history for such condition. On general examination patient had small reddish coloured lesions around the umbilicus, appearing like angiokeratomas. Skin biopsy confirmed the lesion. On enzyme assay his alpha galactosidase activity found to be '0' nmol/hr/mg of protein, confirming his diagnosis. Patient's creatinine and 2 D ECHO were normal and urine had 1+ proteinuria. Patient started on carbamazepine tablets for pain and referred to higher centre for genetic diagnosis and enzyme replacement therapy. CASE REPORT 2: An 18-year-old male referred to our hospital by general practitioner for fatigue and pedal oedema with deranged renal function tests. On history taking patient gave history of severe burning pain in both hands and feet since age of 9 yrs. Patient's general examination revealed hypertension with pallor, pedal oedema along with angiokeratomas in bathing suit distribution. Patient's ultrasonography of kidney revealed bilaterally normal sized kidneys with altered echotexture and urine examination showed fine granular foamy cells with sub nephrotic range proteinuria. 2 D ECHO revealed concentric left ventricular hypertrophy. Skin biopsy report supported the diagnosis of Fabry disease. Patient advised to undergo renal biopsy to confirm Fabry nephropathy but patient denied any further diagnostic workup for nephropathy or Fabry disease. Patient started on conservative treatment and carbamazepine in renal dose given for acroparaesthesias. On discharge patient has been advised to visit higher centre for further diagnostic work up and enzyme replacement therapy.Suspicion of Fabry disease in teenager males presenting with symptoms of burning pain in extremities may lead to early diagnosis and treatment of this condition before occurrences of complications.
- [Treatment of lupus nephritis]. [English Abstract, Journal Article]
- Lijec Vjesn 2014 Jul-Aug; 136(7-8):215-9.
Approximately 50% of patients with systemic lupus erythematosus will develop lupus nephritis. Signs of renal involvement such as proteinuria > or = 0.5 g/24 h especially with glomerular hematuria and/or cellular casts should be an indication for biopsy. Goals of immunosuppressive treatment in lupus nephritis is remission with avoidance of treatment-re- lated harms. Initial treatment for patients with class III (+/- V) and class IV (+/- V) LN are intravenous cyclophosphamide (total dose 3 g over 3 months) or mycophenolate mofetil (or mycophenolic acid) in target dose of 3 g/day for 6 months, always in combination with glucocorticoids, wihile in class V, mycophenolate mofetil in combination with glucocorticoids is recommended. In patients improving after initial treatment, mycophenolate mofetil at lower doses (2 g/day) or azatioprine (2 mg/kg/day), both in combination with low dose prednisone for at least 3 years are recommended. In resistant and relapse cases switch from cyclophosphamide to mycophenolate mofetil, or vice versa, or rituximab is recommended.
- The importance of screening for serum free light chains in suspected cases of multiple myeloma and their impact on the kidney. [JOURNAL ARTICLE]
- BMJ Case Rep 2014.
Multiple myeloma (MM) is the second most common haematological malignancy in the UK. We present a case series of three patients with light chain only myeloma who had normal serum protein electrophoretic studies at screening and were diagnosed using serum and urine free light chain assessment. This series reiterates the importance of thorough and robust screening for MM in patients presenting with renal disease. We review the up to date literature and we highlight the need to screen patients for MM with a combination of serum electrophoresis/immunofixation and either urinary or serum free light chain measurement and to maintain a high index of suspicion regardless of the presence or absence of proteinuria. We also discuss the emerging role of the serum free light chain assay.
- Podocyte dedifferentiation: a specialized process for a specialized cell. [Journal Article, Review]
- Front Endocrinol (Lausanne) 2014.:148.
The podocyte is one of the two cell types that contribute to the formation of the glomerular filtration barrier (GFB). It is a highly specialized cell with a unique structure. The key feature of the podocyte is its foot processes that regularly interdigitate. A structure known as the slit diaphragm can be found bridging the interdigitations. This molecular sieve comprises the final layer of the GFB. It is well accepted that the podocyte is the target cell in the pathogenesis of nephrotic syndrome. In nephrotic syndrome, the GFB no longer restricts the passage of macromolecules and protein is lost into the urine. A number of phenotypic and morphological changes are seen in the diseased podocyte and in the literature these have been described as an epithelial-mesenchymal transition (EMT). However, there is a growing appreciation that this term does not accurately describe the changes that are seen. Definitions of type-2 EMT are based on typical epithelial cells. While the podocyte is known as a visceral epithelial cell, it is not a typical epithelial cell. Moreover, podocytes have several features that are more consistent with mesenchymal cells. Therefore, we suggest that the term podocyte disease transformation is more appropriate.
- Ramipril Lowers Plasma FGF-23 in Patients with Diabetic Nephropathy. [JOURNAL ARTICLE]
- Am J Nephrol 2014 Oct 10; 40(3):208-214.
Background/Aims: Ramipril attenuates renal Fibroblast growth factor-23 (FGF-23) expression, ameliorates proteinuria and normalizes serum phosphate in the diabetic Zucker rat with progressive renal disease suggesting that the renoprotective effect by this drug may be in part due to a FGF-23-lowering effect of angiotensin-converting enzyme (ACE) inhibition. Methods: In this nonrandomized study, we tested whether ACE-inhibition reduces circulating FGF-23 in type-2 diabetics with stage-1 chronic kidney disease (CKD) and proteinuria. Intact FGF-23, the eGFR, proteinuria and the endothelium-dependent flow-mediated (FMD) response to ischemia and other parameters were measured at baseline and after 12-weeks of treatment with ramipril (n = 68) or amlodipine (n = 32). Results: Blood Pressure (BP) fell to a similar extent (p < 0.001) in the two groups. However, 24 h proteinuria and the FMD improved more (both p < 0.01) in ramipril-treated patients than in amlodipine-treated patients. Changes in proteinuria (r = 0.47) and in FMD (r = -0.49) by ramipril were closely associated (p < 0.001) with simultaneous changes in FGF-23 and this link was confirmed in multiple regression analyses. In these analyses, the relationship between FMD and proteinuria changes attained statistical significance (p < 0.01) only in a model excluding FGF-23 suggesting that endothelial dysfunction and FGF-23 share a common pathway conducive to renal damage. Conclusion: Findings in this study contribute to generate the hypothesis that FGF-23 may be implicated in proteinuria and in endothelial dysfunction in diabetic nephropathy (clinicaltrials.gov (NCT01738945)). © 2014 S. Karger AG, Basel.
- Settling the score: stroke prediction in atrial fibrillation. [Editorial]
- J Am Coll Cardiol 2014 Oct 21; 64(16):1666-8.
- Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome. [JOURNAL ARTICLE]
- Cochrane Database Syst Rev 2014 Oct 16.:CD004293.
Idiopathic membranous nephropathy (IMN) is the most common form of nephrotic syndrome in adults. The disease shows a benign or indolent course in the majority of patients, with a rate of spontaneous complete or partial remission of nephrotic syndrome as high as 30% or more. Despite this, 30% to 40% of patients progress toward end-stage kidney disease (ESKD) within five to 15 years. The efficacy and safety of immunosuppression for IMN with nephrotic syndrome are still controversial. This is an update of a Cochrane review first published in 2004.The aim of this review was to evaluate the safety and efficacy of immunosuppressive treatments for adult patients with IMN and nephrotic syndrome. Moreover it was attempted to identify the best therapeutic regimen, when to start immunosuppression and whether the above therapies should be given to all adult patients at high risk of progression to ESKD or only restricted to those with impaired kidney function.We searched Cochrane Renal Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese databases, reference lists of articles, and clinical trial registries to June 2014. We also contacted principal investigators of some of the studies for additional information.Randomised controlled trials (RCTs) investigating the effects of immunosuppression in adults with IMN and nephrotic syndrome.Study selection, data extraction, quality assessment, and data synthesis were performed using the Cochrane-recommended methods. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes.Thirty nine studies with 1825 patients were included, 36 of these could be included in our meta-analyses. The data from two studies could not be extracted and one study was terminated due to poor accrual. Immunosuppression significantly reduced all-cause mortality or risk of ESKD ((15 studies, 791 patients): RR 0.58 (95% CI 0.36 to 0.95, P = 0.03) and risk of ESKD ((15 studies, 791 patients): RR 0.55, 95% CI 0.31 to 0.95, P = 0.03), increased complete or partial remission ((16 studies, 864 patients): RR 1.31, 95% CI 1.01 to 1.70, P = 0.04), and decreased proteinuria ((9 studies,(393 patients): MD -0.95 g/24 h, 95% CI -1.81 to -0.09, P = 0.03) at the end of follow-up (range 6 to 120 months). However this regimen was associated with more discontinuations or hospitalisations ((16 studies, 880 studies): RR 5.35, 95% CI 2.19 to 13.02), P = 0.0002). Combined corticosteroids and alkylating agents significantly reduced death or risk of ESKD ((8 studies, 448 patients): RR 0.44, 95% CI 0.26 to 0.75, P = 0.002) and ESKD ((8 studies, 448 patients): RR 0.45, 95% CI 0.25 to 0.81, P = 0.008), increased complete or partial remission ((7 studies, 422 patients): RR 1.46, 95% CI 1.13 to 1.89, P = 0.004) and complete remission ((7 studies, 422 patients): RR 2.32, 95% CI 1.61 to 3.32, P < 0.00001), and decreased proteinuria ((6 studies, 279 patients): MD -1.25 g/24 h, 95% CI -1.93 to -0.57, P = 0.0003) at the end of follow-up (range 9 to 120 months). In a population with an assumed risk of death or ESKD of 181/1000 patients, this regimen would be expected to reduce the number of patients experiencing death or ESKD to 80/1000 patients (range 47 to 136). In a population with an assumed complete or partial remission of 408/1000 patients, this regimen would be expected to increase the number of patients experiencing complete or partial remission to 596/1000 patients (range 462 to 772). However this combined regimen was associated with a significantly higher risk of discontinuation or hospitalisation due to adverse effects ((4 studies, 303 patients): RR 4.20, 95% CI 1.15 to 15.32, P = 0.03). Whether this combined therapy should be indicated in all adult patients at high risk of progression to ESKD or only restricted to those with deteriorating kidney function still remained unclear. Cyclophosphamide was safer than chlorambucil ((3 studies, 147 patients): RR 0.48, 95% CI 0.26 to 0.90, P = 0.02). There was no clear evidence to support the use of either corticosteroid or alkylating agent monotherapy. Cyclosporine and mycophenolate mofetil failed to show superiority over alkylating agents. Tacrolimus and adrenocorticotropic hormone significantly reduced proteinuria. The numbers of corresponding studies related to tacrolimus, mycophenolate mofetil, adrenocorticotropic hormone, azathioprine, mizoribine, and Tripterygium wilfordii are still too sparse to draw final conclusions.In this update, a combined alkylating agent and corticosteroid regimen had short- and long-term benefits on adult IMN with nephrotic syndrome. Among alkylating agents, cyclophosphamide was safer than chlorambucil. This regimen was significantly associated with more withdrawals or hospitalisations. It should be emphasised that the number of included studies with high-quality design was relatively small and most of included studies did not have adequate follow-up and enough power to assess the prespecified definite endpoints. Although a six-month course of alternating monthly cycles of corticosteroids and cyclophosphamide was recommended by the KDIGO Clinical Practice Guideline 2012 as the initial therapy for adult IMN with nephrotic syndrome, clinicians should inform their patients of the lack of high-quality evidence for these benefits as well as the well-recognised adverse effects of this therapy. Cyclosporine or tacrolimus was recommended by the KDIGO Clinical Practice Guideline 2012 as the alternative regimen for adult IMN with nephrotic syndrome; however, there was no evidence that calcineurin inhibitors could alter the combined outcome of death or ESKD.
- The difficulty in considering modifiable pathology risk factors in children with IgA nephropathy: crescents and timing of renal biopsy. [JOURNAL ARTICLE]
- Pediatr Nephrol 2014 Oct 16.
The need for an early diagnosis of primary IgA nephropathy (IgAN) is particularly felt in children since they have a long life expectancy. However, IgAN has a slowly progressive course and renal function can even remain unchanged for decades. The long-term predictive value of modifiable risk factors, such as proteinuria and proliferative/inflammatory lesion at renal biopsy, remains unknown. Interest has focused on crescents, which represent a clear risk factor for renal vasculitides. A number of rare cases of extracapillary IgAN involving >40 % of glomeruli have been reported, but in most cases of IgAN crescents involve <10 % of glomeruli. The long-term effect of small non-circumferential crescents detected by chance or without a clinical picture of progressive IgAN is still unknown. The Oxford study failed to find a predictive value of crescents in either children or adults, and these results were confirmed by the recent VALIGA study on 1,147 patients with IgAN (174 children). A recent study reports a correlation between the time elapsed from the diagnosis of urinary abnormalities and renal biopsy which suggests that crescents are associated with disease onset and then likely undergo a healing process into sclerotic lesions, which are commonly detected in biopsies performed years after onset. The authors of this study propose that primary IgAN may have similarities with Henoch-Schoenlein purpura nephritis, which presents with acute glomerular damage, mesangial proliferation, endocapillary leucocyte infiltration and crescent formations, and that these lesions can undergo resolution with sclerotic healing. This hypothesis is highly suggestive of the silent progression of several cases of IgAN without clear clinical changes, stressing once more the need for a combined clinical and pathological evaluation of children with IgAN that considers both the underlying pathogenetic event and its possible evolution.