Last Month in Nephrology...by Prof Tukaram Jamale

Written by Meguid El Nahas on Friday, 05 May 2017. Posted in OLA Blog

Last Month in Nephrology...by Prof Tukaram Jamale

April-May 2017

JASN 

Pregnancy outcomes in recovered AKI 

In a study of 105 pregnancies classified as rAKI (pregnant women with history of recovered AKI) were compared with 24640 control pregnancies-authors noted that “past episode of AKI, despite return to normal renal function before pregnancy, associated with meternal adverse outcomes in pregnancy”. Women with r-AKI were more likely to have preterm deliveries and deliveries by cesarean section compared with women without AKI (40% versus 27%; P=0.02). Also rAKI were more likely to have -preeclampsia, preterm preeclampsia, and early preterm preeclampsia (23%, 10%, and 7% versus 4%, 1%, and 0.4%; P<0.001). In offspring of mothers with r-AKI, 40% developed the composite adverse fetal outcome (preterm delivery, NICU admission, small for gestational age, or perinatal death) versus 19% in those without AKI (P<0.001). 

Clear message is -monitor young women with rAKI for maternal and fetal complications if they get pregnant. Don’t jump to the conclusion and blame past AKI for these complications though! Unlike other AKI outcome literature claiming host of bad outcomes associated with AKI in long run, authors of this paper (in addition to acknowledging limitations of  retrospective database analyses) make sensible conclusion,”We, therefore, hypothesize that the underlying metabolic milieu (or other shared risk factors) of these women confers risk for both preeclampsia and AKI.”

Hyponatremia: guidelines on guidelines

‘There are only two tragedies of human life…one, not to get what you want and other is to get it’ said Oscar Wilde. Had he been a nephrologist, he would have said,’there are only two tragedies in the management of hyponatremia…one not to correct it and other is to correct it!’

 Here and here are two guidelines on hyponatremia (european and american) and  this JASN article tries to compile them together. Whatever formula you choose, everyone except serum sodium obeys them.  I remember my residency days when more often than not serum sodium would either not change or change very little or change in opposite direction. Algorithms beginning with  assessment of volume status can only impress your board examiners as differentiation of euvolemic vs hypovolemic hyponatremia by clinical assessment can just be as accurate as toss of coin [sensitivity (50%–80%) and specificity (30%–50%)].

Only test that works at beside is repeated measurements of serum sodium and urine output trend-sudden onset of polyuria being the harbinger of dangerous overcorrection. In elderly, CKD, and for those on thiazides even urine Na can’t be relied upon. 

Some important points:

 -Safety limits have consistently decreased over last two decades from 14-16meq per day to 6-7meq per day given the dangers of overcorrection.

-Fractional excretion of uric acid >12% has the highest sensitivity and specificity to diagnose SIAD (i don’t know who does it)

-Coeptin which is one of the degradation products after prohormone is cleaved to form vasopressin and unlike vasopressin is more stable and can be assayed easily. May make our life easier if it becomes commercially available.

-In severely symptomatic acute hyponatremia, both guidelines prefer bolus 3% saline (100-150ml over 10-20min; can be repeated x3 if needed) over infusion (which is prevalent practice).

-Vaptans are NOT for severely symptomatic or acute hyponatremia; moreover if you overcorrect while using vaptans you lose DDAVP as an option to lower back. Urea on the other hand can be safer and effective option (i dont know how to get it)

CJASN 

“If you can measure it, you can associate it with something” and this issue of CJASN is full of such associations which only rarely turn out to be causal. Serum phosphorus and graft loss, TG/HDL ratio and mortality in dialysismonocyte count and risk of CKD/ESRDCRP and GFR decline to name a few. Time will be better used reading two nice reviews –IgA nephropathy and SGLT2 inhibition. 

SGLT2 inhibitors in addition to glycemic control, have been shown to lower your blood pressure, weight, uric acid, and are the only OHA that showed CV benefit. Also New onset of macroalbuminuria, new onset or worsening of DKD, doubling of serum creatinine and initiation of RRT was less in those treated with SGLT2i. EMPA-REG OUTCOME was funded by Boehringer Ingelheim and Eli Lilly-so lets wait for all of these to be confirmed in more studies. 

Another interesting article on symptom management in CKD: role of dialysis deals with an important puzzle that nephrologist face in patients with stage 4-5 CKD. “The interpretation of the literature is challenging, because the symptoms associated with uremia are often vague, difficult to quantify objectively, and difficult to distinguish from symptoms that can be attributed to conditions coexisting with advanced CKD or side effects of medications used to manage these conditions. Patients with stage 4 or 5 CKD are prescribed a mean of eight different medications” This is  one of the most symptomatic patient population and whether the given symptom complex will be benefited by dialysis is not always simple question to answer. This is especially so in elderly and frail population with multiple other comorbidities and calls for shared decision making involving patient and their caretakers.

Am J Nephrology

Interesting report of 477 patients from Germany who were identified as having euvolemic hyponatremia while on thiazide therapy. No single test could reliably differentiate SIAD from thiazide induced hyponatremia (TIH).  Its commonly believed to be hypovolemic hyponatremia due to saliuresis, but its not the case. Ever wondered why Gitleman’s which is a state akin to chronic thiazide use don’t develop hyponatremia?  Polydipsia and impaired urea mediated free water excretion  are the main drivers of TIH. So whatever may be the cause, be prompt in preventing/treating cerebral edema due to acute hyponatremia (3% saline) and osmotic damage due overcorrection (free water and/or DDAVP). Accompanying editorial nicely summarises the issue of TIH and practical difficulty in differentiating it from SIAD. Here is an excellent blogpost on use of DDAVP in safe correction of hyponatremia.

Nephrology Dialysis Transplantation

Every clinician who is committed to deliver best available care to his patients should  have basic understanding of the research methods to be able to make sense of the ever growing literature. I have found most lectures on research methods by statistician boring and sedating and best way to learn this is to apply/interpret them for articles published in your own specialty. This issue of NDT is devoted to clinical epidemiology and is worth archiving to your desktop. Prediction versus etiologysurvival analysisclinical versus statistical significancerelative versus absolute riskmeta analysis -all of them have examples from nephrology literature that makes it easy to understand the concepts. 

Sildenafil for glomerular disease

Erectile dysfunction turning out to be ‘blessing in disguise’ for patients with diabetic kidney disease! Here is a paper and an editorial (which I tried hard to read full). I was so disappointed when I noted that subjects of this experiment were rats and mice. Sildenafil seems to act via same pathways as pioglitazone which was once advertised as antiproteinuric. Abstract starts with this background “PPAR-γ agonists, like pioglitazone, appear antiproteinuric.” and probably even after human studies sildenafil will have the same place (?) as pioglitazone in the treatment of proteinuria. Meanwhile we can watch what happens to UPCR after somebody ‘gets started’ on Viagra. 

Tukaram Jamale
Associate Professor
Department of Nephrology
Seth GS Medical College and KEM hospital,
Mumbai, India 

 

 

 

Meguid El Nahas

Professor Meguid El Nahas PhD, FRCP

Chief Editor, OLA Director

Professor El Nahas was born in Cairo, Egypt and undertook his undergraduate medical education in...
Posted: 2 months 2 weeks ago by elnahas #21431
elnahas's Avatar
EXCELLENT!
Posted: 2 months 2 weeks ago by elnahas #21432
elnahas's Avatar
Please note that a Sildenafil like Phosphodiesterase 5 inhibitor reduces proteinuria in humans with diabetic nephropathy: www.ncbi.nlm.nih.gov/pubmed/27113485
Posted: 2 months 2 weeks ago by tukaram #21433
tukaram's Avatar
I am clean bowled by Prof Meguid El Nahas
Posted: 2 months 2 weeks ago by elnahas #21434
elnahas's Avatar
Dear Tukaram, to stay in the cricket analogy, your effort in summarising the latest nephrology literature is worthy of a century by the great Sachin Tendulkar...!!!
Posted: 2 months 2 weeks ago by elnahas #21435
elnahas's Avatar
Here is the abstract of our work on PDE5 inhibitor in Diabetic Nephropathy.
This was a Phase 2, proof of Concept clinical trial aiming to test the impact of a Sildenafil-like drug on proteinuria:

J Am Soc Nephrol. 2016 Nov;27(11):3459-3468. Epub 2016 Apr 25.

Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic Nephropathy.

Scheele W, Diamond S, Gale J, Clerin V, Tamimi N, Le V, Walley R, Grover-Páez F, Perros-Huguet C, Rolph T, El Nahas M.

Abstract
Diabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy. In total, 256 subjects with an eGFR between 25 and 60 ml/min per 1.73 m2 and macroalbuminuria defined by a urinary albumin-to-creatinine ratio >300 mg/g, were randomly assigned 3:1, respectively, to receive PF-00489791 (20 mg) or placebo orally, once daily for 12 weeks. Using the predefined primary assessment of efficacy (Bayesian analysis with informative prior), we observed a significant reduction in urinary albumin-to-creatinine ratio of 15.7% (ratio 0.843; 95% credible interval 0.73 to 0.98) in response to the 12-week treatment with PF-00489791 compared with placebo. PF-00489791 was safe and generally well tolerated in this patient population. Most common adverse events were mild in severity and included headache and upper gastrointestinal events. In conclusion, the safety and efficacy profile of PDE5 inhibitor PF-00489791 supports further investigation as a novel therapy to improve renal outcomes in DN.
Posted: 1 month 4 weeks ago by drwazeer1 #21468
drwazeer1's Avatar
Excellent blog.... enjoyed a lot.

Add your comments

Please login in to join the discussion