estudo importantes Flashcards
AKIKI 2
patients: three days of oliguria or anuria or a BUN over 112.
From there patients randomized to standard care would be started on KRT immediately and people in the delayed group would not receive kidney replacement therapy until their BUN was > 140 for a day. 300 de ureia
While the number of KRT free days (the primary outcome) did not differ between groups, there was a statistically significant increased risk of death with the delayed strategy. So delay KRT as long as possible, but not longer than possible.
SSaSS: Potassium Salt In HTN Reduces Stroke and Mortality in NEJM
in rural Chinese population >/= 60 years old with hypertension or has a history of stroke that studied the effect of salt substitute (75% sodium chloride and 25% potassium chloride) compared to use of regular salt (100% sodium chloride) in decreasing cardiovascular events and death. And, oh boy, it did. In a 5-year follow-up period, stroke, major cardiovascular events, and mortality per 1000 patient-years were lower in the salt substitute group. Hyperkalemia was not an issue
AURORA Trial (voclosporin) for Lupus Nephritis in The Lancet
his study was a double-blind, placebo-controlled, randomized clinical trial testing whether the addition of voclosporin to standard treatment of lupus nephritis in adults would improve the proportion of patients achieving complete remission. The authors reported 41% of voclosporin treated patients achieved complete remission at 52 weeks compared to 23% of placebo treated patients (OR 2.65, CI 1.64-4.27, p <0.0001). Adverse events were similar in both groups. Why use voclosporin if other calcineurin inhibitors are already available? One major advantage is that voclosporin does not require trough drug level monitoring which makes it much easier for patients and physicians. One downside is the very high cost.
FIGARO Completes the Finerenone Orchestra (CV Outcomes in DKD) in NEJM
FIGARO enrolled patients with T2DM and either stage 2 to 4 CKD and moderately elevated albuminuria, or stage 1 or 2 CKD and severely increased albuminuria (earlier CKD stages). The primary outcome was cardiovascular; a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. During a median follow-up of 3.4 years, finerenone reduced the risk of composite cardiovascular outcomes (by 13%) driven mainly by reduction in hospitalization for heart failure (by 29%). The study did not meet its secondary composite kidney endpoints, namely kidney failure, a sustained eGFR decrease of at least 40%, or renal death, however, finerenone decreased progression to ESKD. Finerenone did cause slightly more hyperkalemia with a rise in the use of K binders in the active group, and 1.2% hyperkalemia-related discontinuation of the drug (it should be noted that a run-in period actively maximizing RAS inhibition was used).
KDIGO BP 2021 Update: 120 For All
2 major RCTs- SPRINT demonstrated cardiovascular and survival benefits and ACCORD showed decreased risk of stroke when the target SBP was ≤120 mm of Hg. KDIGO 2021 thus recommends aiming at a SBP of ≤120 for all patients with CKD irrespective of albuminuria/proteinuria (exception being patients on dialysis and kidney transplant recipients) - that is if the BP measurement was obtained in a standardized manner. It also recommends a slightly higher target in kidney transplant recipients- SBP≤130 mm Hg and DBP≤80 mm Hg due to lack of evidence of a stricter target and the possible risk of dramatic AKI and graft loss. The guideline also addresses the need for lifestyle interventions to lower BP in CKD while also emphasizing that the DASH diet and potassium based salts may not be appropriate in advanced CKD. In children, KDIGO stands its ground on lowering 24-hour mean arterial pressure (MAP) measured by ambulatory blood pressure monitoring (ABPM) to ≤ 50th percentile for age, sex, and height. Annual ABPM (if unavailable - use standardized auscultatory office BP) followed by 3-6 monthly standardized auscultatory office BP monitoring is recommended thereafter. Lastly, RAS inhibitors are recommended as the first line antihypertensive in patients with CKD of all age groups (in addition to calcium channel blockers in patients with kidney transplants). Overall, the take home message is to standardize BP measurement and achieve a target SBP ≤ 120 mm Hg (with exceptions of course!)
CLICK: Chlorthalidone Reduces BP in CKD in NEJM
a carefully conducted randomized controlled trial of chlorthalidone in advanced CKD for patients with uncontrolled hypertension. CLICK showed that modest doses of chlorthalidone on top of standardized regimen of ACE inhibitor, beta-blocker, calcium channel blocker and loop diuretics are potent agents for uncontrolled blood pressure. Though they lowered the blood pressure effectively, chlorthalidone did cause hypokalemia, hypercalcemia, hyperuricemia, hyponatremia, and orthostatic hypotension, so caution is advised. Patients with advanced CKD are often not invited to major clinical trials and so little of their care is vetted with carefully done clinical trials, so when we get this data it deserves to be a Top Story of 2021.
Keep on Flozin’ing IgA Subgroup of DAPA CKD in KI
270 patients with IgA nephropathy enrolled in the Dapa-CKD trial showed that B again followed A. Specifically, the hazard ratio for the primary outcome (sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from a kidney disease-related or cardiovascular cause) was an impressive 0.29 (95% CI 0.12, 0.73); the mean rate of eGFR decline with dapagliflozin was better than placebo (−3.5 and −4.7 mL/min/year respectively); and dapa reduced the urinary ACR by 26% relative to placebo. Purists (and those with financial interests in ongoing trials of novel drugs for IgA nephropathy) have pointed out that this wasn’t a trial designed specifically to examine patients with IgA, and that in an often slowly progressive disease a 2.1 year median follow up time could be extended, but this is another big feather in the cap of the SGLT2 inhibitors in the treatment of proteinuric CKD of any cause.
New eGFR Equations: Remove Race in eGFR Equations in NEJM
he task force recommended that all eGFR calculations be derived from the 2021 CKD EPI equation without a race variable. The task force also recommended increased use of cystatin C. It is important to emphatically state that race is a socio-political construct and not a biologic or genetic determinant.
PERL and CKD-FIX- Urate lowering in CKD
aiming to answer the age old question of whether uric acid is simply a marker of CKD or contributes to the progression of CKD. First, the PERL study enrolled adult patients with type 1 diabetes, a serum urate level of 4.5 or greater, and eGFR of 40-99.9 ml/min/1.73m2 and randomized them to treatment with allopurinol or placebo for 3 years. After a 2 month washout, the primary outcome of baseline adjusted iohexol GFR was essentially the same in both groups. The second study, CKD-FIX, enrolled adults with CKD stage 3 or 4 with either an albumin/creatinine ratio of ≥265mg/g OR an eGFR decline of at least 3ml/min/1.73m2/year and randomized them to receive allopurinol or placebo. There was no difference between groups in the primary outcome of change in eGFR over 2 years. There was a significant decrease in serum urate levels in both studies, however no changes in kidney outcomes.
FIDELIO- Finerenone in DKD
was the largest diabetic kidney disease ever done. Fidelio was a multicenter, placebo-controlled, international, randomized trial of fineronone, a novel, non-steroidal aldosterone antagonist. This unusual drug gives up what was previously aldosterone antagonists’ strongest asset, an almost uncanny ability to treat resistant hypertension (see PATHWAY-2) while retaining aldosterone antagonists’ Achilles heel, the tendency to cause hyperkalemia (see AMBER). But despite this curious combination attributes, finerenone was able to reduce the progression of diabetic kidney disease in patients on maximum ACEi or ARB. Look for finerenone to try to get approval by the FDA in 2021 and add to the expanding options in the treatment of diabetic kidney.
PEXIVAS- Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis
The perceived negative outcome of the trial was that plasma exchange was not really superior to standard of care. This result is going to be sliced, diced, and analyzed in many different ways for years to come. There has already been a debate in the pages of NDT (Pro: Kronbichler et al, NDT 2020; CON: Specks et al, NDT 2020) , but the interested reader should also read this review (de Vriese et al, CJASN 2020) which examines all the excuses for still continuing plasma exchange, such as the lack of kidney biopsy results, or active disease, or severe pulmonary hemorrhage, and lays them to rest. At the most, there may be a possibility that it buys you a few months of dialysis freedom, which is transient and is washed away in the long-term follow-up. However, lost in the plasma exchange discussion is a far more important result:lower dose steroids are just as efficacious, and far more safe than the standard dose of steroids used until now. Infections are a common cause of mortality in ANCA vasculitis, to repeat ourselves
STARRT AKI- Early versus late dialysis in AKI
More than 3000 patients were randomized to starting dialysis when clinically indicated (standard) or earlier (accelerated strategy), on the basis of development of biochemical AKI (see the NephJC summary for the detailed discussion of eligibility and clinician ‘veto’). Not only was there no advantage of starting early, but more patients in the early arm remained dialysis dependent. Starting dialysis early in AKI is not helpful and it is harmful. Large trials are where biological plausibility and observational studies come to die
ALTITUDE
alisquireno + bra/ieca aumentou risco de hiperk
The addition of aliskiren to standard therapy with renin–angiotensin system block-ade in patients with type 2 diabetes who are at high risk for cardiovascular andrenal events is not supported by these data and may even be harmful.
ontarget
terapia combinada ieca + bra
aumentou morte, dialise e dobro da creat
2015 - EMPAREG
POST HOC
diminuiu almbuminuria, risco de progressao para ESKD em 50%
e taxa de declinio da fc renal
estudos dm
ISGLT2
KDIGO GN 2021 Update in KI
IgA nephropathy-cool calculators- New QxMD calculator to assess with prognosis based on the MEST-C scoring system. It’s available for pediatric patients too.
RAS inhibitors are still the first line of choice, if proteinuria persists, can consider a 6 month course of steroids.
Membranous nephropathy & its unpronounceable antigens- biopsy is not needed for diagnosis in patients that present with nephrotic syndrome and positive Anti-PLA2R antibody. Also, anti-PLA2R antibody levels should be used to guide therapy. Treatment is based on disease severity- Rituximab in moderate to severe risk and Cyclophosphamide & steroids in severe to very severe risk population.
Nephrotic Syndrome in Children:8-12 weeks of steroids are comparable to 24 weeks of steroids. In frequent relapsers, consider switching to steroid-sparing agents.
Minimal change disease in adults- No major change here: Biopsy is recommended. Steroids are the first choice unless contraindicated.
FSGS in adults- new classification: New 4 classes- primary, secondary, genetic, and undetermined cause (FSGS-UC). For FSGS lesions on biopsy with NS features, likely primary, treat with steroids otherwise evaluate for secondary causes and monitor.
Immunoglobulin/ Complement-mediated GN- stop calling it MPGN:
3 classes- Ig/ immune-complex mediated GN (ICGN),
complement-mediated GN,
membranoproliferative pattern without immune complexes or complement.
Therapy is tailored based on severity and not all patients need immunosuppression. RAS inhibitors rule again as the first line.
Anti-Neutrophil cytoplasmic antibodies (ANCA)- associated vasculitis- another melody here: reduced dose steroids are as effective as high dose (PEXIVAS); plasma exchange (PLEX) is not recommended unless there are anti-GBM antibodies. Prefer rituximab unless there is a severe disease (cyclophosphamide). Maintenance therapy should be based on clinical course, not on biomarkers
. Lupus Nephritis- more changes to come soon: Induction therapy is similar to 2012 guidelines, with a lower cumulative dose of IV and oral steroids and replacement of NIH cyclophosphamide regimen with Euro-lupus protocol.
PROLIFERATIVE III E IV +/- V , REQUIRE LESS CORTICOIDENewer drugs like Voclosporin (AURORA trial) POUPADOR DE CORTICOIDE and Belimumab (BLISS-LN) have shown promising results. Mycophenolate mofetil (MMF) is still the first line for the maintenance regimen.
Anti-glomerular basement membrane (Anti-GBM) antibody GN- same guidelines: Treat promptly, even before the biopsy. PLEX is recommended until antibody titers are undetectable. For patients on dialysis, particularly those with >85% crescents, whose risks of immunosuppression may be higher, consider conservative management. Overall, these guidelines recommend the usage of fewer steroids across the spectrum of GN and have clarified and modified several classifications.
