Prof. Bassam Saeed blogged:
New KDIGO guidelines for IgA nephropathy
Immunosuppressants should only be considered in high risk patients after optimizing supportive measures.
• We suggest that patients with persistent proteinuria ≥1 g/d, despite three to six months of optimised supportive care (including ACE-I or ARBs and BP control) and GFR >50 ml/min, receive a six-month course of corticosteroid therapy
Immunosuppressive agents (cyclophosphamide, azathioprine, MMF, cyclosporine)
• We suggest not treating with corticosteroids combined with cyclophosphamide or azathioprine in IgAN patients (unless there is crescentic IgAN with rapidly deteriorating kidney function
• We suggest not using Immunosuppressive therapy in patients with GFR <30 ml/min unless there is crescentic IgAN with rapidly deteriorating kidney function
• We suggest not using MMF in IgAN
Atypical forms of IgAN
• We suggest using steroids and cyclophosphamide in patients with IgAN and rapidly progressive crescentic IgAN (Defined as IgAN with crescents in more than 50 % of glomeruli in the renal biopsy with rapidly progressive renal deterioration), analogous to the treatment of ANCA vasculitis.
From these guidelines it is clear that immunosuppression should only be considered in high risk patients after supportive measures have been optimized
If immunosuppression is considered, the only recommended approach is corticosteroid monotherapy for six months.
Adam from Paris for GKA 2010
The Theme of this 1st Episode:
Back to Old drugs: Aza, MTx, Hydroxychlorquene.
Less Corticosteroids still do the same action with less S/Es.
Cr Nadir is earlier than Albumin one.
Date: Thursday May 24th 2012
08:30 - 12:30 CME Courses
Rheumatology for nephrologists 46
Peritoneal Dialysis Workshop 47
Title: Rheumatology for nephrologists
Chair: Hans-Joachim Anders, Munich, Germany
David Jayne, Cambridge, UK
i. Welcome and introduction
Hans-Joachim Anders, Munich, Germany
David Jayne, Cambridge, UK
ii. Joint pain in CKD patients: When do we need a joint aspirate?
Hendrik Schulze-Koops, Munich, Germany
1) Sodiumaurate Crystals in Gout is different that those of CPPD crystals in Pseudo gout which may occur in the dialysis population.
2) The Take Home message in unclear monoarthrits; Do Not Wait; and do Aspirate; however;
3) Synovial fluid aspirate is a sterile procedure; however; the risk of complication by sepsis is 1/10,000; which cost a famous German athelet his career by causing septic arthritis for a procedure which is considered in his case may not be justified.
iii. Proteinuria in the patient with arthritis
Volker Vielhauer, Munich, Germany
4) Proteinuria in patients with arthritis include these following 5 main Topics: either Association, Complication, Manifestation, Toxicity and the fifth and the Last but not the least is Co-morbidity.
5) This need Reply: A 34 yrs old male diagnosed as Behcet and was on CsA and CS. Developed proteinuria 2.8 g/24hrs, Cr 88um/L, with Dysmorphic RBCs, Hence referred to the Nephrologist; with a Bx showed IgA in A Behcet Disease with eGFR 60 ml, with no Cresents and no Fibrosis. How to manage? Opinions so to tell you what happen and what they did?
6) Assoicated Renal Disease in Behcet include mainly Amyloidosis 69/156, and GN in 51/152 cases. IgA deposition was found in 22% of GN with Behcet.
7) Associated Renal Disease in RA include: Mesangial GN 40/110, Renal Amyloidosis 33/110 and MN 19/110 cases.
8) The 2012 “standard of care” in lupus nephritis – referral,
drugs and monitoring
Frédéric A. Houssiau, Brussels, Belgium
8) LN is a very heterogenous disease which varies from single shot, or relapsing 1/3 or refractory 1/5 of the cases.
9) Poor prognostic factors include many; but on the top of the lists are Race (AA), non-observance to Rx, Absence of primary response to IS.
10) Poor prognostic factors in the pathology; beyond Roman numerals include fibrinoid necrosis, partial cresents and circumferential cresents.
11) Renal Bx is not a routine procedure in all SLE patients. However; Low C3, High Anti-DNA, or renal involvements include Pr > 0.5 g/24hrs and/or Active sediment are red flagged.
12) You may need Renal Bx so as not to miss APL-related Disease.
13) Which LN patients should be immunosuppressed? Class I, II NO ---, III & IV (both have Endo/extra capillary cellularity and sub-endo ID: YES ---, V in Selected Cases. However; wait for
my 2nd Episode from the EDTA concerning ISN/RPS 2003 Classification for more Info and critic by Ian Roberts.
14) LN: Towards no Steroid regimen? By Imperial College of Kidney and Tx Institute in London UK; by Liz Lighstone et al. Giving on Day 1 and 15th : 500 mg MPS + 1g RTx. Then only use MMF with no steroids. Claiming optimal renal protection.
15) Euro Lupus Nephritis Trial showed LD is equivalent to HD of CYP for induction in LN.
16) The cost of MMF is more than 10 times that of CYP for induction of Rx in LN.
17) Both AZA and MMF have similar effect as maintenance Rx for LN as proved by two trials ALMS (David Wafsy; especially if the two arms were induction with IV CYP) and MAINTAIN.
18) Never forget Plaquanil (Hydrochlorequene) in LN not only in SLE. Nephrologists are reluctant to consider it.
19) This need Reply: A Pregnant Lady with Acute flare of SLE; which IS Rx you recommend? Either with or without LN? and Do you recommend Abortion to save the mother from being ESRD or more complication?
v. Non-renal flares in lupus nephritis patients – new options
Falk Hiepe, Berlin, Germany
20) Bortezomib can cause clinical improvement in severe and refractoy SLE. This proteasome inhibition markedly reduced plasmablasts and plasma cells from the peripheral blood and bone marrow.
David Jayne, Cambridge, UK
viii. ANCA-associated vasculitis - an update on therapeutic
Alan Salama, London, UK
Wait for my 2nd Episode of the Pathology.
The Theme is:
New Pathological Dx with still invalid clinical Significance.
Recent pathological classification of LN 2003 are more confusing than older one and may be wrong.
Criteriae necessary for Dx may not be necessary anymore. (ABMR with C4d –ve).
Wait for my 3rd Episode of the Opening Cermony and Pioneers in European Nephrology .
The Theme is:
There are two "REFRAINS" in the opening Cermony: Continuity and Memory.
Modesty and The Patient is what Kept the Pioneers so Pioneers.
Dr Alaa Sabry blogged:
ERA/EDTA Friday activity Update : Polycystic Kidney Disease: clinical studies:
1-Vaptans in ADPKD (Professor Vicente Torres):
Discussed the pathogenesis of PKD and the contribution of increased CAM in the cyst growth and diseases progression with plenty of evidences and its role in upregualtion of PKD activity and possible role V2R antagonists in the treatment –The design of TEMPO study ( Tolvaptan Efficacy and Safety in Management of CKD and Outcomes ) the group received Tolvaptan showed decrease in TKV – total kidney volume- was well tolerated.
Data analysis for the result of Tempo 3-4 study is going and result is expected late 2012.
Just as we thought the ONTARGET trial ended all speculation about dual blockade with ACEI and ARB being beneficial, another study reported by a Spanish group showed once again that there is no benefit from dual blockade.
Results from the COSMOS study were reported today. This is an observational, non interventional study comparing the outcomes of patients treated with phosphate binders compared to those not received any binders. It is a nulti-centre study that compared the outcomes of some 4500 patients from 220 centres who received binders to 2000 patients who didn't. Those treated with binders had a better survival.
Clearly a lot of money has been invested to show that if you have low phosphate not needing binders you are probably elderly, frail and malnourished with likely poor outcome. In fact the authors admit that the non-binder group were older.
I am sure we will have many drug reps knocking on our doors telling us how phosphate binders save lives!
Dr Alaas Sabry blogged:
ERA/EDTA precongress CME course - Renal Pathology- an interesting course, the following topics were presented:
1-New insight in C3 glomerulopathy ( Terry cook- Imerial college London) THE PATHOPHYSIOLOGY AND CLASSIFICATION OF THIS TYPE OF NEPHROPATHY , RENAL PATHOLOGY AND FUTURE TREATMENT OPTIONS- CASE REPORTS FOR THE VALUE OF ECULIZUMAB IN TREATMENT OF C3 NEPHROPATHY
2-Critical review of the ISN/RPS LN Classification (IAN ROBERTS , OXFORD ,UK) :
Excellent comparative presentation with WHO classification and the reperoducability of ISN/RPS classification
3- Update in renal Tx biobsy ; stress on C4d negative , microvascular injury ( capilaritis) positive AMR and the future value of Endothelial Cell Associated Transcripts (ENDATA ) was elaborated.
So last week I saw 2 patients within a few hours each of whom tells their own story. The first was in transplant clinic. She was transplanted 10 years ago and has perfect kidney function. Her BMI was 40 at the time of transplant and is now 50. She sailed through the transplant without any technical or imunnological problems. Transplantation was undoubtedly a life-saver – she had factor V Leiden mutation and was running out of access due to recurrent clotting of access.
In the afternoon I saw a 50 year old patient on haemodialysis. She had a BMI of 35 and had previously been active on the transplant list. She was otherwise well with no other significant comorbidity. She was reviewed by a surgeon who felt that as she had significant central obesity, transplantation would be technically challenging and so she was suspended from the list until her BMI was 30. She asked to see me as she was in a terrible state. She was literally starving herself and had lost 8Kg but needed to lose a further 8 kg before her BMI hit the magic 30. She pleaded for me to be reactivated on the transplant list though I explained this was ultimately a surgical decision. What was clear was that i) I had never seen her look so ill as she did now she was trying to lose weight and ii) for her to maintain herself at a BMI of 30 she would need to continue to starve herself.
So these two cases prompted me to look a bit at the literature around obesity and transplantation and the following themes emerged:
- While it has long been recognised that higher BMI associates with survival on dialysis there is also some data to suggest that weight loss is harmful. Molnar and colleagues looked at over 14000 wait listed dialysis patients and found that those who had loss greater than 5Kg had a death hazard ratio of 1.51. Of course this doesn’t mean necessarily that intentional weight loss is harmful but it is food for thought when telling dialysis patients to lose weight.
- Whilst surgical complications post transplantation ( e.g. wound infections) do increase with BMI, the data on the effect of obesity on graft survival is conflicting. Streja and colleagues analysed10,090 kidney transplant recipients were followed for up to 6 years posttransplantation. Low pretransplant BMI (<22 kg/m2) showed a trend toward higher posttransplant mortality, whereas obesity (BMI ≥ 30 kg/m2) was not associated with mortality, albeit it showed a trend toward higher graft loss. A smaller analysis of over 1000 patients showed recipient BMI to correlate with delayed graft function which of course in itself is a risk factor for poorer graft survival. In a 20 year follow up of around 1800 patients from Holland, BMI increment post transplantation and BMI at one year were both much more powerful predictors of adverse graft and patient survival than pre-transplant BMI. Indeed pretransplant BMI didn’t have a statistically significant association with adverse outcomes
- The key question perhaps isn’t whether the obese are more likely to run into complications but whether they still have a survival advantage from transplantation. In an analysis of around 7000 patients who had a BMI of >30 who were wait listed for transplantation, the incidence of mortality in those who underwent transplantation was still less than half of those who stayed on dialysis waiting for a kidney. The beneficial effect of transplantation was lost when BMI>41
So what to do? Well given the fact that the safety of weight loss isn’t established in dialysis patients (and may be harmful in some patients) we need to be honest with patients and tell them that we don’t know whether this is safe - it may well be safe to lose weight but it may not be and so we need to tell patients that. There is no evidence to show that weight loss pre-transplant improves outcomes post-transplant and the observational data seems to suggest that patients with a pre-transplant BMI of upto 40 still gain a survival benefit from transplantation. Therefore as ever we need to make individual decisions on a holistic evaluation of the patient taking into account all other comorbidities rather than plucking arbitrary numbers and targets out of the air. This is of course only opinion but I'm not convinced that the patient with a BMI of 35 who is currently starving herself to get to a BMI of 30, will get any health benefit from such starvation.
Associations of body mass index and weight loss with mortality in transplant-waitlisted maintenance hemodialysis patients. Molnar MZ, Streja E, Kovesdy CP, Bunnapradist S, Sampaio MS, Jing J, Krishnan M, Nissenson AR, Danovitch GM, Kalantar-Zadeh K. Am J Transplant. 2011 Apr;11(4):725-36
Associations of pretransplant weight and muscle mass with mortality in renal transplant recipients. Streja E, Molnar MZ, Kovesdy CP, Bunnapradist S, Jing J, Nissenson AR, Mucsi I, Danovitch GM, Kalantar-Zadeh K. Clin J Am Soc Nephrol. 2011 Jun;6(6):1463-73.
Recipient and donor body mass index as important risk factors for delayed kidney graft function. Transplantation. 2012 Mar 15;93(5):524-9.Weissenbacher A, Jara M, Ulmer H, Biebl M, Bösmüller C, Schneeberger S, Mayer G, Pratschke J, Öllinger R.
Effect of obesity on the outcome of kidney transplantation: a 20-year follow-up.Hoogeveen EK, Aalten J, Rothman KJ, Roodnat JI, Mallat MJ, Borm G, Weimar W, Hoitsma AJ, de Fijter JW. Transplantation. 2011 Apr 27;91(8):869-74.
An interesting pilot, proof of concept study is published in JASN online today looking at the role of renal dennervation in patients with resistatnt hypertension and CKD. In the last couple of years a number of studies have suggested that renal dennervation maybe useful in the management of resistant hypertension and larger scale clinical trials are currently underway to test this hypothesis. As yet however there have been no studies in the CKD population. The rationale is that there is increased renal sympathetic activation in CKD and further that activation of the renal afferent sympathetic system in response to CKD also increases central sympathetic activation. Renal denervation involves placing a radiofrequency catheter in the renal artery ( accessed by femoral artery) to allow ablation of renal sympathetic chain.
In this study by Hering and colleagues from Melbourne, 15 patients with CKD 3/4, a mean office BP of around 174/9, taking an average of 5.6 drugs underwent the procedure. At follow up that is between 3-12 months there was no difference in creatine-based eGFR or cystatin C suggesting that the procedure has no adverse effects on kidney function. Mean changes in office systolic and diastolic BP at 1, 3, 6, and 12 months were −34/−14, −25/−11, −32/−15, and −33/−19 mmHg, respectively. Interestingly and perhaps disappointingly the mean 24 hour BP and daytime BP didnt change. However there was a significant reduction in nightime systolic BP on 24 hour monitoring falling from a mean of 154 to 144mmHg at 6 months. i.e. there was a restoration of nightime dipping of BP - lack of nightime dipping is a stronger predictor of CV events than daytime BP. Interestingly there was no significant change in the number of medications being taken at the end of the study. The lack of effect on daytime BP is not easily explainable but the numbers are of course small and there is substantial intrpatient variability. Peripheral arterial stiffness as assessed by augmentation index was significantly reduced at 3 months suggesting that the effect on blood pressure was real. There were reductions in proteinuria, BNP and increases in hamegloblin at 3 months but these did not reach statistical significance.
Theres clearly a long way to go before we know whether this technique will impact on meaningful outcomes but in CKD but as the authors say this preliminary study provides guidance for the design of further cinical trials to evaluate the short and long term effects of the technique in CKD.