Concept Map: Hypertension in Hemodialysis

 

This is a schematic of the treatment of resistant HTN in the hemodialysis patient. Based on a review published in JASN

Figure made using biorender.com 

Vaccines and the Renal patient- COVID19

As vaccines are arriving at a rapid rate (historic) for SARs-COv2, most of the United States is still dealing with a larger more deadlier wave of infections. Hospitals at most of the US are again at a standstill with what we had seen in March, April in NY. 

mRNA vaccine.. we are not used to that technology in the medical world. While reading more on this topic, I found this simplified version by Dr Daniel Goldstein, CT surgeon at Montefiore and a well known voice of COVID care on Linkedin. I have made some changes and additions to his thoughts. 

mRNA Vaccines: A primer
The process, simplified:

1. Use DNA, enzymes to create the mRNA sequence that codes for part of SARSCoV2 spike protein
2. Attach 5’cap, poly-A tail and UTRs for stability and better translation
3. Purify and get rid of reagents, enzymes other additives
4. Encapsulate in lipid nanoparticle (phospholipids, PEG, cholesterol) to protect and facilitate delivery into cells.
5. Store in cold (or extremely cold) until use
6. Inject intramuscularly (2 shots, 3-4 wks apart)
7. Encapsulated mRNA taken up by muscles cells.
8. mRNA released into cytoplasm where protein building machinery (ribosomes) will bind to it sequentially and produce many spike proteins. Average 20 sec - couple of mins to make one protein
9. mRNA has half-life about 10 hrs. Sufficient to make lots of protein. Eventually broken down by RNAses.
10. Protein is bound to cell surface where it is recognized as foreign by immune system
11. Ab production, and Ag specific memory B cells and T follicular helper cells are produced
12. More robust response of the above with 2nd injection as body has been “primed”

Advantages of mRNA vaccine:
1. Non-infectious
2. Doesn’t insert into DNA (nucleus).
3. Half life, immunogenicity and delivery can be regulated
4. Quick to make

Disadvantages to me: Seem none, except it's a new technology. 

Well we are in a pandemic with a new deadly virus- I would roll those shirts and get the vaccine. What is the data on our renal patients.- Essentially none. 

ESKD patients:

To my knowledge, ESKD patients were not in the large vaccine trials but these are vulnerable populations. The UK released a statement of the patients who are most vulnerable in nephrology. 

Renal Transplant patients:

Although initial clinical trials of COVID-19 vaccines did not include immunosuppressed patients, we would expect the vaccines to offer protection against COVID-19 infection in these extremely vulnerable patients. An effective COVID-19 vaccine should reduce staff and patient infection resulting in lower rates of serious illness and death. What is interesting as few studies done during the pandemic showed that the renal transplant patients do have a good immune response to the virus( not a lowered one).  Studies from Germany and the US showed decent antibody converting. This suggests that vaccines would work in the organ transplant patients and provide amazing protection.

CKD and patients with autoimmune glomerular diseases: No data exists but vaccines would be helpful here as well.

Nephrology community awaits the arrival of the vaccines...

2020: What a year for Nephrology

As we enter the end of 2020( finally), we are starting to see some hope for the vaccines as a lifeline as we enter the rising COVID-19 surge.  For nephrology, 2020 has been a positive and negative year. 

Let's start with the negatives:
1. Covid19 led to development of more AKI than we had imagined and several of those patients dying as a result. Very few survived the RRT-related AKI
2. Our dialysis patients had a tough battle leading to an increased mortality
3. Many transplant centers were on hold and several on the wait list had a high mortality and so did some of our transplant patients.
4. All conferences and meetings were virtual( taking away the networking opportunity for many)
5. All fellowship interviews went virtual( hard to assess candidates candidly)
6. Research ( non covid19) came to a halt and or was interrupted 

But there is a silver lining to the COVID19 pandemic for nephrology:

1. Increased data and outcomes research on AKI as a result of the pandemic
2. Rise of HOME dialysis ( which was dormant for years) came more to the forefront( including acute PD)
3. Rise of the Nephrologists as front line COVID19 warriors leading to perhaps more applications this year
4. SGLT2i studies infiltrating NEJM multiple times making a mark on diabetic and non diabetic kidney disease
5. Novel therapeutics in autoimmune renal diseases are on a rise
6. Virtual conferences allowed for more quicker and swifter transfer of knowledge ( and more attendance)
7. Collaboration on research rose super fast with trials such as STOP-COVID
8. Gender and Ethnic diversity was evident in Kidney week this year and kept it's strength in 2020
9. More incentives and compensations increases for nephrologists will reign in 2021
10. Increase interest in subspecialization in Nephrology 

Topic Discussion: ESRD patients and COVID-19

While we saw several rising cases of AKI associated with COVID-19, the ESKD population was also vulnerable to this virus. With COVID-19, we didn't know if we would see worsening effects on ESRD or beneficial ( given a not so robust immune system in ESRD).  But the proximity and being in a closed dialysis unit did put most of them at risk. 

Studies from China and Europe on ESKD patients with COVID-19 were limited to small numbers and single centers. One of the first studies from US from CUMC was limited by less then 100 patients as well. It did show poor outcomes of 59 patients where 31% had died.

A Study from UK did discuss the concerns for an urban dialysis center ( on risk of hospitalizations). Of 1530 patients (median age 66 years; 58.2% men) receiving dialysis, 300 (19.6%) developed COVID-19 infection, creating a large demand for isolated outpatient dialysis and inpatient beds. An analysis that included 1219 patients attending satellite dialysis clinics found that older age was a risk factor for infection. COVID-19 infection was substantially more likely to occur among patients on in-center dialysis compared with those dialyzing at home. 

A study from the Bronx in NY also showed poor outcomes for hospitalized ESKD patients. Elevated inflammatory markers were associated with in hospital death.

Another UK study also found a high prevalence of seropositivity in the outpatient dialysis units. 

Alberici et al.describe their clinical experience with MHD patients cared for at 4 outpatient dialysis facilities that are part of the Brescia Renal COVID Task Force. In a period of 1 month, viral positivity was detected in 94 of their 643 ESRD HD patients (15%). Important findings in the study were the mild form of symptomatology at presentation, the high rate of overall mortality (29%), and emergence of usual risk factors for mortality and acute respiratory distress syndrome in SARS-CoV-2–positive HD patients. In addition, although certain patients were deemed more stable and were managed in the outpatient facility, 3 of those subsequently died, and a substantial portion had significant worsening of their symptoms.

Goicoechea et al. describe the clinical course and outcomes of 36 patients from 2 dialysis facilities caring for 282 patients that were admitted to a tertiary hospital in Madrid based on positive reverse transcription polymerase chain reaction for SARS-CoV-2. They report a mortality rate of 30.5%, and 33% of their patients required mechanical ventilation. 

At our health system of over 23 hospitals in NY, we decided to compare the outcomes of ESKD patients to non ESKD patients. The data was from 13 hospitals and our final cohort had 419 (4%) with ESKD and 10,063 (96%) without ESKD.This is the largest study to date.

What did we find:( similar tweetorial by first author Jia Ng)

I want to share our new paper “Outcomes of patients with ESKD hospitalized with COVID-19”. @kidney_int @hofstrakidney @hofstramed @jam_hirsch @rimdamyeloma @mala_sachdeva @sfishbane @kdjhaveri Susana Hong

https://t.co/B2jd3RO4lt
[THREAD] pic.twitter.com/4S03hTRHAo

— Jia Hwei Ng, MD, MSCE (@jiahweing) August 16, 2020

1. Patients with ESKD were older, had a greater percentage self-identified as Black, and more comorbid conditions.

2. Patients with ESKD had a higher rate of in-hospital death than those without (31.7% vs 25.4%), odds ratio 1.38, 95% confidence interval 1.12 - 1.70). This increase rate remained after adjusting for demographic and comorbid conditions (adjusted odds ratio 1.37, 1.09 - 1.73).

3. Patients with ESKD had similar rates of mechanical ventilation as those without ESKD (89 [21.2%] vs 2076 [20.6%]). There was no difference in the odds of mechanical ventilation between the groups.

4. The odds of length of stay of seven or more days was higher in the group with compared to the group without ESKD in both the crude (1.62, 95%CI 1.27 - 2.06) and in the adjusted analysis (1.57, 95% 1.22 - 2.02)

5. We conducted stratified analyses to investigate the risk factors of death in the subgroups of ESKD and the non-ESKD separately, with the hypothesis that the risk factors of death and the magnitude of risk factors would differ between the two groups.

6. For patients without ESKD, the independent risk factors for in-hospital death increased age, male sex, cardiovascular disease, cancer, requiring ventilation, requiring vasoactive meds, high blood urea nitrogen, low albumin, high CRP and high ferritin.

7. The diagnosis of hypertension and use of an ACE inhibitor or ARB were associated with a lower risk of in-hospital death in the non-ESKD group.

8. Among patients with ESKD, independent risk factors for in-hospital death were increased age, requiring ventilation and lymphopenia, elevated BUN and high serum ferritin. Black race was associated with a significantly lower risk of death among patients with ESKD.

9. The protective effect of HTN in the non-EKSD group, and the protective effect of Black race in the ESKD group defy easy explanation. Perhaps APOL1 has some protective cardiac effect?

10. This is a large cohort of hospitalized patients with #COVID-19 comparing ESKD and non-ESKD in a diverse patient population. We had prespecified operational definitions for exposures, covariates and outcomes, as well as rigorous adjudication by two independent reviewers for ESKD exposure.

11. What limitations do we have?--Despite the larger size of this study compared to other reports, the ESKD sample may still have been relatively underpowered to find other statistically significant risk factors in mortality. Also there was inability to adjust for remdesivir and dexamethasone. As the evidence of these 2 drugs came after the surge of #COVID-19 cases in our health system, only a small proportion of patients received these drugs.

12. We had 11 PD patients in our admitted cohort. This was also published in a special report as well. Of 419 hospitalized patients with ESKD, 11 were on chronic PD therapy (2.6%). Among those 11, 3 patients required mechanical ventilation, 2 of whom died. Of the entire cohort, 9 of the 11 patients (82%) were discharged alive. While fever was a common presentation, more than half of our patients also presented with diarrhea. Interestingly, 3 patients were diagnosed with culture-negative peritonitis during their hospitalization. Seven patients reported positive SARS-CoV-2 exposure from a member of their household.

In conclusion, among patients hospitalized with COVID-19, those with ESKD had a higher rate of in-hospital death compared to those without ESKD. 

Two recent studies also show the outpatient HD infection and admission rates. A study published in AJKD from Canada showed from universal screening, 4.6% were infected. 

Another French study in KI showed a low incidence of infection of 3.3% in a large >40,000 dialysis patients. Older age, low albumin, and cardiac disease were risk factors for mortality. 

Taken together, the results suggest both a need for further research and the continued need for careful infection control procedures in the ESKD population at risk for #COVID-19.

Topic Discussion: COVID-19 and hemodialysis patients

As we all learn more and more about COVID-19, the burning question in many nephrologists is the risk to patients on dialysis mainly in-center HD? While we all are developing guidelines of how to triage and place patients on in-center HD who have symptoms of COVID-19, what is their risk of severe infection vs. death from this virus compared to the general population?

So far, while we are still learning about the Italian, South Korean, Japanese experience, the only pre published data is from Wuhan, China dialysis units. Ma et al describe their experience and it is quite interesting what they found.

Brief summary of the study

1. It is a single HD unit epidemic course of infected patients compared to non infected and staff that were effected.
2. Of 230 HD patients, 37 were infected( 37%) and 2 medical staff of 33 staff members. During that time frame, the HD center had 7 deaths, 6 were COVID-19 positive patients. This made the mortality of 3%( higher than usual for that dialysis unit)
3. Presumed cause of death was hyperkalemia and cardiac events and not pulmonary cause
4. 62% were men, mean age 66 years.
5. 59% patients had bilateral CT scan involvement, 41% had unilateral findings
6. Serum levels of all cytokines measured( Il-4,6,10, TNF .etc) were lower levels compared to non HD patients with COVID-19
7. In their discussion, they do mention that the deaths were due to under-dialysis and hyperkalemia given the fear of contracting the virus-- interesting analysis.
8. Interestingly, none of the 37 patients in their center were admitted to the ICU due to severe PNA
9. The authors think that the HD patients don't mount a severe immune response and don't have that cytokine storm as seen in healthy adults leading to the "itis" leading to less organ damage.

This study is a start. More data from S.Korea, USA, Japan and Italy might help us in better information to decide on the care of the HD patient with COVID-19

Recently also, there is a case report published on HD patient treated successfully with anti virals in China in Kidney Medicine

Topic Discussion: COVID-19 and the Kidney

Coronavirus disease 2019 (COVID-19) causes a severe acute respiratory syndrome. Similar to SARS outbreak, this virus has caused the 2019-2020 outbreak. It presents with a dry cough, fever, running nose, fatigue and shortness of breath. The elderly, hx of pulmonary disease, immunocompromised are at risk. Mortality rate is around 2-3% from ongoing outbreaks. 

How does this virus affect the Kidney. First and foremost, what is the data on transmission via dialysis units and infection in dialysis patients. Wuhan, China was where the outbreak occurred and started. In a single center study under open access review, 37 cases ( 16%) of HD patients were infected. 7 HD patients died and 6 had COVID-19 during this epidemic. The precaution measures taken by HD units prevented further cases. For some unclear reason, while HD patients were more likely to get this infection, the cases were milder than non HD counterparts. 

Here is the ASN suggestions for HD units for COVID-19 screening and precautions.

What about AKI? Is it common?  Again from Wuhan, in the month of the major outbreak in China, < 20 patients showed mild elevations in BUN and crt and trace albuminuria. 5 patients required CRRT. 
All patients that had CKD after this survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without renal illness before, and one patient had a positive for SARS-CoV-2  from 5 cases with CKD. Interpretation Acute renal impairment was uncommon in COVID-19. SARS-CoV-2 infection does not significantly cause obvious acute renal injury, or aggravate CKD in the COVID-19 patients.

Interestingly, another center reported a different finding.  A large tertiary center in China studied 710 consecutive COVID19 patients, 89 (12.3%) of whom died in hospital. On admission, 44% of patients have proteinuria hematuria and 26.9% have hematuria, and the prevalence of elevated serum creatinine and blood urea nitrogen were 15.5% and 14.1% respectively. During the study period, AKI occurred in 3.2% patients. Kaplan-Meier analysis demonstrated that patients with kidney impairment have higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated serum creatinine, elevated urea nitrogen, AKI, proteinuria and hematuria was an independent risk factor for in-hospital death after adjusting for age, sex, disease severity, leukocyte count and lymphocyte count. Conclusion: The prevalence of kidney impairment (hematuria, proteinuria and kidney dysfunction) in hospitalized COVID-19 patients was high. After adjustment for confounders, kidney impairment indicators were associated with higher risk of in-hospital death. This was in strike contrast to the prior study.

Finally, hypokalemia was a common electrolyte finding in these patients. One would think GI cause as the cause, but GI symptoms were not associated with hypokalemia among 108 hypokalemia patients. Body temperature, CK, CK-MB, LDH, and CRP were significantly associated with the severity of hypokalemia. 93% of severe and critically ill patients had hypokalemia which was most common among elevated CK, CK-MB, LDH, and CRP. Urine K+ loss was the primary cause of hypokalemia.

Anti Hypertensive Agents and removal by Hemodialysis

Here is a list of common anti hypertensive agents used in ESRD and clearance via HD. In general, ACEI are removed in variable amounts, ARBs and aldo antagonists are not. Beta blockers are variable. CCB are variable but in general not that removed.

Class			%Removal with hemodialysis
Angiotensin converting enzyme inhibitors
Captopril			Yes
Benazepril			20–50%
Enalapril			35%
Fosinopril			<10%
Lisinopril			50%
Quinapril    Ramipril			<10%( limited data) <30%
Angiotensin receptor blockers
Losartan			None
Candesartan			None
Eprosartan			None
Telmisartan			None
Valsartan			None
Irbesartan			None
Aldosterone antagonists
Spironolactonea			None
Eplerenoneb			None
Renin inhibitor
Aliskiren			?
β-Blockers and combined α- and β-blockers
Atenolol			75%
Metoprolol			High
Metoprolol XL			High
Propranolol			<5%
Carvedilol			None
Carvedilol CR			None
Labetalol			<1%
Calcium channel blockers
Amlodipine			None
Diltiazem			<30%
Nifedipine			Low
Nicardipine			?
Felodipine			No
Verapamil			Low
Alpha-adrenergic blockers
Doxazosinc			None
Terazosin			None
Prazosin			?
Other
Clonidine			<5%
Hydralazine			None
Isosorbide dinitrate			Yes
Minoxidil			Partially

Topic Discussion: Novel ways to combat Intradialytic hypotension

Intradialytic hypotension(IDH) during hemodialysis(HD) is a challenging clinical concern and often hard to treat.  After one has ruled out cardiac disorder ( especially diastolic dysfunction), common medications and ideas attempted are: midodrine pre dialysis, low temperature during dialysis, daily short dialysis sessions, florinef use, steroids in the right clinical setting, and sodium and or calcium profiling.  Switching to peritoneal dialysis can be an option as well.  The KDOQI guidelines recommends most of these above mentioned changes.

What are some other novel mechanisms that can be used?

1.Carnitine:  Carnitine deficiency has been associated with IDH and trial of L-carnitine at 20mg/kg with dialysis might help reduce IDH


2.Sertraline: This anti- depressant has shown improvement in orthostatic hypotension. Both retrospective and prospective studies in small number of patients demonstrated that treatment with sertraline hydrochloride was associated with an improvement in the hemodynamic parameters in patients with IDH. A recent randomized control trial from Iran also showed good benefit with this agent in IDH. The dose one can usually start is 50mg once a day and then max at 100mg daily per most trials when used for IDH.

Some good references:

https://www.ncbi.nlm.nih.gov/pubmed/26174461
https://www.ncbi.nlm.nih.gov/pubmed/15012700
https://www.ncbi.nlm.nih.gov/pubmed/9531178

3.DDAVP

Rho et al nicely demonstrated in a CJASN paper in 2008 that IDH patients experienced greater decreases in both systolic and diastolic blood pressure during the dialysis session despite equivalent ultrafiltration in both groups. AVP concentration did not increase in the IDH patients compared with controls despite hypotensive episodes. As a result, many have tried to use DDAVP as a treatment option for IDH.
As early as 1990s, vasopressin was tried in 6 patients to help IDH in one single center study with success.  The largest study(17 patients) using this was from Iran. In that study, the treatment arm received intranasal DDAVP (two puffs) 30 minutes before all HD.  Hypotensive episode occurred 18 times (8.82%) in vasopressin group compared with 125 times (61.27%) in placebo group and there was a significant association between them (p=0.0001). In addition mean arterial blood pressure in vasopressin group was 80.77 and in placebo group was 73.92 and also there was a significant association (p=0.0001). The mean Kt/v in group 1 and 2 were 1.29 and 1.28 without any differences between them (p=0.896). This might be another interesting option to consider in IDH.  Risk of  thrombotic events might be something to think about.

4.Droxidopa

This agent has been approved by FDA for autonomic neuropathy.. The trade name is Northera. Droxidopa is a synthetic amino acid precursor which acts as a prodrug to the neurotransmitter norepinephrine. Unlike norepinephrine, droxidopa is capable of crossing the protective blood–brain barrier. Why in IDH? Well recently published trial that was a placebo controlled, phase 2 study looked at efficacy and safety of this agent in IDH.  The investigators looked at placebo vs 400mg vs 600mg dose.  Increase in droxidopa intra-HD MAP were not significantly different from placebo, although droxidopa groups showed significant improvements in mean SBP after HD of +4.8 ± 11.6 mm Hg (600-mg) and +3.4 ± 13.1 (400-mg) compared with -4.4 ± 17.9 mm Hg in placebo, and the drop seen in mean nadir SBP pre- to intra-HD was also reduced. HD terminations decreased 5-fold in the 600-mg group and 2-fold in the 400-mg group, whereas the number of discontinuations stayed unchanged in the placebo group. Treatment of both dosages were well tolerated. This might be an interesting option as well. The most common side effects noted were GI related. 

TOPIC DISCUSSION: Mnemonic for toxins that are removed by hemodialysis

Toxins that are removed by hemodialysis

Here is a mnemonic I found online

I   STUMBLE

I = Isopropanol
S= Salicylates
T = Theophyline
U = Uremia
M= Methanol
B= Barbituates, beta blockers (water soluble ones such as atenolol)
L= Lithium
E= Ethylene glycol

Source: http://crashingpatient.com/toxicology/general-toxicology-random-drugs.htm/

Nephrology Crosswords: Hemodialysis

Check out the next installment of Nephrology Crosswords in Kidney International on
Hemodialysis

Consult Rounds: Dialysis in the Acute Brain Injury patient

Standard hemodialysis can increase cerebral water content and lead to edema. The pressure in the brain or ICP shouldn’t have too many influences.  There is strong buffer system in the brain but if that fails- then the ICP can increase rapidly.  It has been noted that even small subclinical cerebral edema that occurs in IHD can slowly raise the ICP.  Why is that and how does the BP and acidosis make this possible?

A review by Davenport on this topic suggests few cautions:

1.      Drops in blood pressure or intradialytic hypotension can lead to ICP rises( Figure 1 from the Davenport review)

2.      Big fluctuations in urea shifting

3.      Intracellular acidosis in the brain as CO2 is removed in dialysis leads to paradoxical Co2 absorption in the brain and causing imbalance.

4.      Exogenous substances can enter brain ( albumin) during brain injury as BBB is broken and lead to worsening edema.

Above Figure from Davenport article.

Some key points regarding what should be done then?

1.         All standard intermittent therapies, hemofiltration, hemodialysis, and hemodiafiltration, will lead to increased cerebral swelling, and if the patient has suffered a severe injury and is unconscious, then most centers would deem continuous renal replacement or hybrid therapies as the preferred treatment. ICPs have shown to remain much more preserved and constant in CRRT forms rather than IHD forms of therapy.

2.         Treatment should be designed to both slow down the rate of change of serum urea and osmolality, and to maintain cardiovascular stability( so perhaps daily IHD might be needed to minimize BUN shifts and prevent edema from getting worse)

3.         Given breakdown of BBB, avoid heparin based dialysis in this setting

4.         If doing HD, would do daily and use a lower BFR and cooler dialysate( 35C), smaller dialyzer and high Na bath(≤10 mEq/L above serum sodium), bicarb of 30meq/l , higher K and calcium baths).

5.         Some might suggest keeping a pre dialysis BUN low( less osmotic shifts – close to 30 and keep on supplemental oxygen.

Interestingly, regarding cooled dialysis- a recent JASN 2014 article sheds some light on that as well. In total, 73 patients on incident hemodialysis starting within 6 months were randomized to dialyze with a dialysate temperature of either 37°C or 0.5°C below the core body temperature and followed up for 1 year. Cooled dialysate improved hemodynamic tolerability, and changes in brain white matter were associated with hemodynamic instability and patients who dialyzed at 0.5°C below core body temperature exhibited complete protection against white matter changes at 1 year.

Preventing hypotension and rapid osmotic shifts is essentially what is required. 

Twice weekly, three times weekly or daily dialysis- where do we stand?

While observational trials had shown that there is much more benefit in daily dialysis (improved phos control, better HTN control, anemia), the FHN trial in NEJM proved some of the hunch that more dialysis was better in terms of cardiac remodeling and quality of life. This study compared in center patients to standard HD vs daily dialysis.  These were prevalent patients and not incident patients with some residual renal function.  

A recent editorial in AJKD sheds some light on residual renal function as an important predictor of renal survival.  The authors suggest that thrice weekly might rapidly decline renal function compared to perhaps twice a weekly dialysis sessions. But does that matter compared to cardiac outcomes.  The second FHN trial in Kidney international showed that the more intensive nocturnal HD group failed to show benefit compared to the three times a week dialysis.  Interestingly, this was in all incident patients with residual renal function.  The study found that the more intensive HD group lost residual renal function faster and in addition no difference in cardiac remodeling and quality of life. More vascular interventions were also performed in the more intensive arm. 

Finally, the most recent AJN article published this week, a single center study from China shows that twice a week HD preserves residual renal function.  They examined 85 HD patients; 30 of them were initiated with twice-weekly HD for 6 months or longer and 55 patients were started and maintained on thrice-weekly HD treatment. Then a subcohort study in 48 incident HD patients was implemented to assess the independent risk factors responsible for RKF decline during the first year of HD therapy. Clinical outcomes were the same in both groups. The multivariate analysis showed that factors such as the male gender, HD frequency, URR and intradialytic hypotension episode were associated with residual renal function loss. This study’s main outcome was residual renal function and not mortality.  It will be interesting to see and follow these patients to see the mortality data regarding this.

What does this lead us to believe? One size DOES NOT fit all. Perhaps initially, HD should be catered to preserving residual renal function and start slowly. Some patients might require twice a week HD, some three times a week and some perhaps more such as 4-6 times a week.  Should we be doing HD just as we do PD? When we calculate PD related CRCL, we use the residual renal function clearance and then the peritoneal clearance and add them to get to our expected/desired kt/v.  Why shouldn’t we do that in HD as well?  Incident patients might benefit from less intensive HD and prevalent patients who have lost residual renal function, might benefit from more intensive HD.  More studies are needed to answer these questions that the FHN and other studies have raise. 

Atenolol or Lisinopril: and the winner is….HDPAL update

Hypertension in dialysis patients is hard to manage. In over 90% of the cases, the cause of volume. Salt and water intake and inability for fluid removal remains the most like cause of HTN in ESRD. Few cases are renin mediated as well.  Which anti hypertensive medications have the best effect in the few cases of HTN that is not treated with volume removal?  ACEI/ARB would be the most obvious choice. Randomized trials in non ESRD hypertensive patients have shown that LVH is significantly improved and preventing cardiac morbidity and mortality with ACEI/ARBs compared to Beta Blockers.  A recent study in NDT 2014 by Agarwal et al. was a randomized trial of atenolol and lisinopril in ESRD patients(HDPAL).

Results:

1.       Monthly blood pressures were higher in ACEI group after initiation of therapy

2.       More serious cardiovascular events occurred in ACEI group compared to the atenolol group

3.       All cause hospitalizations were higher in ACEI group as well

4.       Finally, LVH had improvement equally in both groups

5.       These results hold most true for black patients.

Some interesting points:

1.       This is the first study to look at head to head drug comparison in ESRD patients with BP management

2.       Counter to what may have shown in non ESRD patients, this study showed that atenolol was better.

3.       Atenolol is renally cleared of all the beta blockers and number of patients that are non anuric might matter as it might have had more clearance and less of a heart rate effect. Interestingly, that variable was well matched as well.

4.       Although not sure of significance, less atenolol patients had coronary artery disease and significant number of them had re vascularization procedures. This may be a big weakness as going into the study, there were less sicker patients in the ACEI arm from a cardiac perspective.

5.       But to counter balance that, there were more males in the atenolol arm compared to ACEI arm

6.       Increased fractures were noted with atenolol arm- perhaps again getting into the renal clearance effect perhaps and effect on heart rate and causing blocks

7.       There was no placebo arm and most patients were black – perhaps hard then to generalize to all races.

8.       Using BP monitoring interdialytic ambulatory BP monitors was a strength

9.       Interestingly, it says at the end of the manuscript: received for publication Dec 2^nd 2013 and accepted in revised form on Dec 4^th 2013.  That is strange that a paper can get peer reviewed, revised and gotten back for accepted form in 2 days. Hopefully that was a typo.