Tag: dialysis

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CJSAN Article on CKD care and 1st year survival on dialysis

The Nephrology Blog has an interesting post on early nephrology referral of CKD patients and outcome on dialysis. I pulled all the references from that paper which have looked at the subject. I’ll be adding my thouhts on these references over next few pages so that this post becomes a quasi review article or annotated reference list.

Hasegawa et al. Greater First-Year Survival on Hemodialysis in Facilities in Which Patients Are Provided Earlier and More Frequent Pre-nephrology Visits. Clin J Am Soc Nephrol (2009) 4 595-602. (PDF)

  • DOPPS I and II databases
  • 8500 new starts to dialysis
  • Pre-ESRD Nephrology contact defined as at least one visit prior to HD
  • PNV associated with adjusted odds ratio of 0.57! (half the risk of death for one visit! what a bargain!) p<0.001
  • adjusted for age, sex, race, primary cause of ESRD, 14 summary comorbidities (CAD, CHF, other cardiac disease, htn, dm, cerebroVD, PAD, cancer, HIV/AIDS, lung disease, neurologic disorders, GI bleeding, recurrent cellulitis/gangrene)
  • Facility level data is consistent with the individual patient data. DOPPS always tries to show this because it controls for some of the biases inherent in a retrospective study. From the ESRD NephSap:

  • When we choose to examine facility practice using statistical models, patients are assigned not to the individual treatment received but to the facility’s practice (e.g., percentage of patients receiving vitamin D or having phosphorus within guideline range). Patient- or facility-level outcomes can be used. The rationale for this method is fundamental to the DOPPS and merits additional emphasis here. In standard observational analyses, the true effect of a treatment of interest may be distorted analytically by the effect of the indication to receive that treatment (treatment-by-indication bias). This bias is a fundamental challenge to inferring the causal effect of a treatment from observational data. The DOPPS facility practice-based analytic approach is conceptually similar to instrumental variable analysis, a method embraced for decades in econometrics and now used more commonly in clinical studies to address treatment-by-indication bias (9,10). The approach seeks to identify natural experiments in which patients are nearly “randomly” assigned to a particular facility practice by factors independent of clinical characteristics, such as proximity to the patient’s residence. Ideally, this mimics randomized treatment assignment in a clinical trial. Recent publications discussed theoretical considerations and provided examples in clinical medicine outside nephrology (9 –17).

  • They found a dose effect of frequency of seeing a nephrologist. seeing a nephro doc 5 times had 28% lower mortality than if they saw one once or less.
  • The people with nephrology care were more likely to be diabetic and hypertensive but were less likely to have CHF, lung disease or cancer
  • Nephrology care was also linked to marriage, employment and college educated
  • The creatinine at initiation of dialysis was lower with CKD care 7.2 versus 7.6. [Of note: with creatinines that high, a change of 0.4 only represents a difference of 1 mL/min (9 mL/min with predialysis care, 8 mL/min without)]

Innes et al. Early deaths on renal replacement therapy: the need for early nephrological referral. Nephrol Dial Transplant (1992) vol. 7 (6) pp. 467-71.

Forty-four patients who commenced renal replacement therapy between January 1983 and January 1988 died within 1 year of starting treatment. To examine the factors influencing early mortality of patients on renal replacement therapy these patients (group A) were compared with a group of 44 age- and sex-matched subjects who started dialysis over the same period and who survived more than 1 year (group B). The interval between first presentation and dialysis was significantly shorter in group A (median 36 days) than group B (median 30 months) patients. Plasma urea and creatinine were significantly greater in group A than group B at the time of first presentation to a nephrologist but not at first dialysis. Patients in group A were more often treated first by hemodialysis. Systemic disease as the cause of renal failure did not appear to influence early death. Early death on renal replacement therapy appears to be associated with late referral to a nephrologist. Early referral may be beneficial because it allows for planning of dialysis and treatment of the complications of progressive uremia.

  • 44 patients who died in the first year of dialysis (group A)
  • Compared to 44 patients (age and sex matched) who survived the first year of dialysis (group B)
  • Association found with early death and late referral to a nephrologist. Average time between first visit to nephrologist and initiation of dialysis 36 days in group A and 30 months in group B.
  • no difference in BUN or Cr at initiation of dialysis

Sesso et al. Late diagnosis of chronic renal failure. Braz J Med Biol Res (1996) vol. 29 (11) pp. 1473-8.

BACKGROUND: Recent observations in our country have shown that late diagnosis of chronic renal failure (CRF) is an important cause of late referral and late commencement of maintenance dialysis. We prospectively investigated the influence of late diagnosis of CRF on patient mortality during dialysis therapy. METHODS: Among 184 consecutive patients with nondiabetic end-stage renal disease starting chronic dialysis at the Federal University Hospital in the city of São Paulo, 106 had a late diagnosis of CRF (less than 1 month before starting dialysis) and 78 had an early diagnosis. During the first 6 months of dialysis treatment, patient survival was compared in the two groups, using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Six-month patient survival rate was lower in the late than in the early diagnosis group (69% versus 87%, P less than 0.01). In the late diagnosis group, the hazard ratio of mortality was 2.77 (95% CI, 1.36-5.66) times that of the early diagnosis group. In a multivariate analysis, after adjusting for age, comorbid illness, and serum biochemical measurements, time of diagnosis did not remain significantly associated with mortality risk. In this analysis, age, pulmonary infection, and low serum albumin were significant predictors of mortality. CONCLUSIONS: Patients with a late diagnosis have a higher mortality risk during the first 6 months of maintenance dialysis. This increased risk is related to comorbid conditions, some of which could be prevented by predialysis care. Interventions to promote early diagnosis of CRF and adequate predialysis follow-up need to be evaluated if the survival of patients with chronic renal failure is to improve.

  • 184 new dialysis patients
  • Lack of pre-ESRD CKD care defined as initiation of dialysis within 1 month of the first visit to the nephrologist
  • 6-month rather than 1 year analysis
  • raw mortality was 31% for late dx and 13% for early diagnosis
  • HR for death in the first 6 months of dialysis with late diagnosis was 2.77
  • Despite a very high hazard ratio with late diagnosis, this was not an independent association such that after controlling for age, comorbid illness and biochemical measurments the time of diagnosis was not significant.

Jungers et al. Longer duration of predialysis nephrological care is associated with improved long-term survival of dialysis patients. Nephrol Dial Transplant (2001) vol. 16 (12) pp. 2357-64. (PDF)

  • 1057 consecutive patients
  • pre-dialysis nephrology care less than 6 months in 258 patients (193 of them initiated within a month of the first nephro encounter.)
  • 6-35 months in 267 patients
  • 36-71 months in 227 patients
  • over 71 months in 307 patients
  • mean age 54
  • only 13% diabetics (French study), little hypertension
  • half of the late presentation group had been referred earlier but had neglected or refused nephrological care
  • DM, PVD, HTN, CVD all were more prevelant with late referral
  • Cr was higher in late referral [We need to worry about systemic lead time bias]
  • Dramatic changes in the rates of catheter use and the length of hospital stay associate dwith the initiation of dialysis. Importantly the authors excluded 60 patients who had either AKI or RPGN which precluded prolonged pre-dialysis care.
  • one-year mortality was 13.6% for less than 6 months pre-dialysis nephrocare and 7.4% (6-35 mo), 7.2% (36-71 mo) and 2.5% (over 71 mo) for longer care
  • With multivariate analysis only the longest duration of care (over 71 mo) was significantly and independantly associated with survival with a RR of death of 0.56 p=0.002.
  • The two shorter periods barely missed signifigance: 6-35 mo RR=0.73, p=0.058 and 36-71 mo RR=0.71, p=0.066.
  • Age, DM and prior CVD were each significant with multivariate analysis

Kinchen et al. The timing of specialist evaluation in chronic kidney disease and mortality. Annals of Internal Medicine (2002) vol. 137 (6) pp. 479-86. (PDF)

  • 828 new on-set ESRD from 81 centers
  • time from first visit to initiation of dialysis
  • Late: less than 4 months
  • Intermediate: 4-12 months
  • Early: over 12 months
  • 213 patients were eliminated because of a lack of definitive medical records
  • Significantly associated with late referral was Black ethnicity, not attending college, not having insurance, PD, not having DM, less urine output, lower renal function, less exercise, more anemia, lower albumin, less ESA, less vascular access.
  • Late referral was associated with death
  • Notice how quickly the Late and Early curves digress. By 10 months it looks like the association is maximal and the curves are roughly parallel after that.
  • The association with timing of referral and mortality was robust and remained significant when examined with 5 recipes for controlling different factors:

  • An interesting finding was that late referral was worse for patients with diabetes and hypertension, growing segments of the ESRD population
  • Sicker patients were referred later begging the question does the sickness prevent the consultation or does lack of nephrologic care cause other co-morbid diseases to become more severe (i.e. better use of diuretics in a heart failure patient, sometimes the nephrologist is the only one still willing to use ACEi with a GFR of 18)

Roderick et al. Late referral for end-stage renal disease: a region-wide survey in the south west of England. Nephrol Dial Transplant (2002) vol. 17 (7) pp. 1252-9. (PDF)

  • 361 of 411 in England
  • Late within 4 months
  • Late’ within 1 month
  • 35% within 4 months
  • 23% within 1 month
  • Again late referrals were older, sicker, had less accesses
  • 33% Six-month mortality with less than 1 month versus 16% for longer than a month
  • A late referral occured in 60% of patients with an established diagnosis of CKD for more than year (preventing the physcian or patinet from excusing themselves by stating “I didn’t know.”)
  • Again the cr was higher at initiation (10.7 versus 9.4 mg/dl) for late referrals.
  • Time of referral was not an independent predictor of survival at 6 months in regression analysis (p=0.293)
  • The only interesting figure comes from the discussion where the authors graph the rates of Late referrals in the medical literature and make a case that it is getting better.

Kessler et al. Impact of nephrology referral on early and midterm outcomes in ESRD: EPidémiologie de l’Insuffisance REnale chronique terminale en Lorraine (EPIREL): results of a 2-year, prospective, community-based study. Am J Kidney Dis (2003) vol. 42 (3) pp. 474-85 (PDF)

Stack. Impact of timing of nephrology referral and pre-ESRD care on mortality risk among new ESRD patients in the United States. Am J Kidney Dis (2003) vol. 41 (2) pp. 310-8. (PDF)

Winkelmayer et al. A propensity analysis of late versus early nephrologist referral and mortality on dialysis. J Am Soc Nephrol (2003) vol. 14 (2) pp. 486-92. (PDF)

Kazmi et al. Late nephrology referral and mortality among patients with end-stage renal disease: a propensity score analysis. Nephrol Dial Transplant (2004) vol. 19 (7) pp. 1808-14. (PDF)

Khan et al. Does predialysis nephrology care influence patient survival after initiation of dialysis?. Kidney Int (2005) vol. 67 (3) pp. 1038-46.

BACKGROUND: Early nephrology referral of patients with chronic kidney disease (CKD) has been suggested to reduce mortality after initiation of dialysis. This retrospective cohort study of incident dialysis patients between 1995 and 1998 was performed to address the association between frequency of nephrology care during the 24 months before initiation of dialysis and first-year mortality after initiation of dialysis. METHODS: Patient data were obtained from the Centers for Medicare & Medicaid Services. Patients who started dialysis between 1995 and 1998, and were Medicare-eligible for at least 24 months before initiation of dialysis, were included. One or more nephrology visits during a month was considered a month of nephrology care (MNC). RESULTS: Of the total 109,321 patients, only 50% had received nephrology care during the 24 months before initiation of dialysis. Overall, first-year mortality after initiation of dialysis was 36%. Cardiac disease was the major cause of mortality (46%). After adjusting for comorbidity, higher mortality was associated with increasing age (HR, 1.04 per year increase; 95% CI, 1.03 to 1.04) and more frequent visits to generalists (HR, 1.009 per visit increase; 95% CI, 1.003 to 1.014) and specialists (HR, 1.012 per visit increase; 95% CI, 1.011 to 1.013). Compared to patients with >/=3 MNC in the six months before initiation of dialysis, higher mortality was observed among those with no MNC during the 24 months before initiation of dialysis (HR, 1.51; 95% CI, 1.45 to 1.58), no MNC during the six months before initiation of dialysis (HR, 1.28; 95% CI, 1.20 to 1.36), and one or two MNC during the six months before initiation of dialysis (HR, 1.23; 95% CI, 1.18 to 1.29). CONCLUSION: Nephrology care before dialysis is important, and consistency of care in the immediate six months before dialysis is a predictor of mortality. Consistent nephrology care may be more important than previously thought, particularly because the frequency and severity of CKD complications increase as patients approach dialysis.

Schwenger et al. Late referral–a major cause of poor outcome in the very elderly dialysis patient. Nephrol Dial Transplant (2006) vol. 21 (4) pp. 962-7. (PDF)

Schmidt et al. Early referral and its impact on emergent first dialyses, health care costs, and outcome. Am J Kidney Dis (1998) vol. 32 (2) pp. 278-83. [negative trial] (PDF)

Roubicek et al. Timing of nephrology referral: influence on mortality and morbidity. Am J Kidney Dis (2000) vol. 36 (1) pp. 35-41. [negative trial] (PDF)

Avorn. ( )

Zhao et al. Physician access and early nephrology care in elderly patients with end-stage renal disease. Kidney Int (2008) vol. 74 (12) pp. 1596-602 (PDF)

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Comment on the latest MDRD article and the state of clinical nephro research

Last Thursday in journal club we reviewed the latest data on protein restriction and progression of CKD.

The best summery of the results are provided at the end of the paper:

…a very low-protein diet increased the risk of death in long-term follow-up of the MDRD Study, but had no impact on delaying the progression to kidney failure…

Imagine that the primary results had been different. Imagine for a moment that the MDRD study, rather than being one of the first of the large, NIH-sponsored, negative clinical trials in nephrology, was instead a great success. Imagine that the very-low-protein diets resulted in a delay of dialysis of 20% compared to a low protein diet and that a low-protein diet resulted in a 25% delay in progression compared to a normal-protein diet. Imagine a universe where protein restriction is the ACE inhibitors of our universe.

Now imagine if this most recent analysis came out in that universe. The above quote in this imagined universe would read something like:

…a very low-protein diet increased the risk of death in long-term follow-up of the MDRD Study, despite successfully delaying the progression to kidney failure…

How would we as a nephrology community come to terms with the fact that our primary intervention that we were advocating in a thousand CKD clinics across the land, was actually killing our patients after they start dialysis. Imagine the hand wringing as we start to realize that we were able to delay dialysis from 12 months to 18 months but at the cost of a doubling of their first year mortality from 22% to 40%.

I would be horrified and stop advocating it in my clinic but lots of my patients would adopt the low protein strategy, essentially play the lottery that this radical change in diet would allow them to escape their fate.

We as the nephrology community need to demand better research. This study stands alone (nearly? or completely?) by looking at a pre-dialysis intervention but measuring the outcome in dialysis. This study goes over the wall separating chronic kidney disease research from dialysis research. We need a name for this x-ray vision of looking through the artificial barrier between CKD and dialysis. I propose transitional research.

We need to demand that our CKD research does this. This distinction is less important when looking at CKD 3 where only 1% go on to dialysis; but when looking at CKD4 patients we need to know how that intervention affects dialysis survival. In CKD 4, 18% of patients will end up on dialysis in 5 years. (D. Keith’s data, PDF)

Which of today’s avant garde treatment of CKD results in a doubling of dialysis mortality?

  • Use of active vitamin D to treat secondary hyperparathyroidism
  • Treatment of anemia with ESAs
  • Use of phos binders, calcium based or otherwise
  • Bariatric surgery
  • Aggressive control of blood sugar

None of these “standard” therapies has been examined with an eye on total mortality before and after initiation of dialysis. We need the definitive studies so at some time in the future we don’t have to tell a patient’s family that the pills we have been prescribing may actually have caused the stroke or heart attack or cancer or…

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Dialysis report card

One of my 81 year old patients just recently started on dialysis. I took care of her CKD for about 3 years before she needed to start dialysis. Today, we had a care meeting and she told me that she was doing great on dialysis and her labs verified this.

Her pastor reads all the good report cards that the kids in her church bring to him. So she brought in her dialysis report card and her pastor read it on Sunday.

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Journal Club: low protein diet

Effect of a very low protein diet on outcome: long-term follow-up.

This is the long-term follow-up of the B group from the original MDRD study.
Enrollment criteria:
  • Age: 18-70
  • Abnormal Cr 1.2-7 women 1.4-7 in men.
  • MAP of 125 or less (160/100)
  • Proteinuria less than 10g per day
  • No diabetics
GFR 13-24 mL/min for the B study (low protein versus very low protein diet). Higher GFR were enrolled in the A study (normal protein versus low protein diet).
Protein was restricted for 3 years.
9 months after the study every nutritional parameter was the same between the two groups.

The primary end-point was a composite of death or dialysis and just about every patient in both groups (95.7%) reached this end-point preventing a separation between the groups (p=0.5). Likewise there was no separation with regards to time to dialysis (p=0.4).

The surprising finding occurs when they looked at death after the initiation of dialysis. There were 34 deaths in the very low-protein group and 19 deaths in the low-protein group (p=0.01).

The separation begins around 15 months and grows over time. This difference was statistically significant and grew to a 2-fold increased risk of death after 6 years.

My take is this fits well with what I tell my patients when they ask me about protein restriction. I have always counseled patients against protein restriction. The two largest RCT were both negative trials (The Modification of Diet in Renal Disease and the Northern Italian Cooperative Study Group). Additionally my patients do not have the benefit of dedicated and repeated nutritional couseling that the patients in these trials receive. My fear is that with little therapeutic upside there is signifigent risk of malnutrition from overzealous protein restriction.

This study probably does not apply to my worry as I doubt patients would adhere to a very low-protein diet.

My other concearn regarding low-protein diets is patients need to get calories from somewhere. Calories can only come from protein, carbohydrates or fat. Considering that the vast majority of CKD patients are destined to die before dialysis I worry that my advice for protein restriction will result in increased carbohydrates (bad for diabetes and possibly CV disease, see Richard Johnson’s fructose hypertension research) and/or increased fats (bad for CV disease) and enhance the risk of death from the more likely outcome.

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Monday was the highest traffic day on this site. Ever.

My post on Everything I learned in fellowship is wrong was featured on the home page of renalWEB.

It feels weird that my post was listed at the top under “News Headlines.” The ATN article came out in July and I just got around to writing about it six months later. I wrote it so that when I discuss the findings on rounds, I have a way to quickly find an abstract of the study with my personal observations. And I will discuss it with the fellows because even though the study was a negative study it is a benchmark study in nephrology. The article is a negative study but it is negative in the way that HEMO was negative, not the way that DCOR was.

  • HEMO is usually listed as a disappointing study because we were not able to help patients by ratcheting up their dose of dialysis from 1.16 to 1.53 (eKt/V).
    But as Glen Chertow argued persuasively, the HEMO trial was a triumph of evidence based medicine. We were able to definitively argue against the desire to incrementally enhance three-times a week day-time dialysis. The increasing evidence for daily and in-center nocturnal dialysis are by-products of the failure of HEMO. If HEMO had been a positive trial we would probably be focusing on a HEMO II with a targetted eKt/V of 1.8. The negative result has sparked innovation and a search for novel ideas.
  • DCOR on the other hand has almost nothing definitive to show despite being “the largest outcomes study ever done in the hemodialysis population.” The failure of DCOR can be attributed to a low event rate, a high but undefined cross-over rate and a 50% drop-out rate. All of these conspired to produce an under-powered study and clinicians are left in a sea of phosphorous binder marketing without near term hope for better guidance.

So the negative finding of the ATN group advances the science of nephrology, removes an important question and will allow us to move on to new strategies to help patients with acute kidney injury.

A final note to the editor of RenalWEB, my bullet on the dose of dialysis referred to the HEMO trial, which did not look at frequency of dialysis or radical increases in dose. The jury is still out on those techniques but I’m with you. Those two strategies seem right and beneficial.

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Dose of DIalysis

Everything I learned in fellowship has turned out wrong. When I was a fellow I was taught:

  • Higher Kt/V were beneficial for patients
  • Increasing the hemoglobin reduced LVH and improved outcomes in CKD
  • Using non-calcium based binders saved lives
  • and most importantly: increasing the dose of dialysis in AKI improved survival

The last point was an area that was emphasized in my education. I heard Dr. Murray spend so much time going over the preliminary evidence that I was honed to proselytize the gospel of early and often dialysis for acute kidney injury. I loved working with Murray, he’s a great speaker, a great teacher and the only man with more board certifications than years in middle school (internal medicine, nephrology, critical care, clinical pharmacology).

Since finishing fellowship it has been humbling watching each of these truths fall to the blade of the RCT (though I still believe that calcium based binders are harmful).

The results of the ATN Trial this past summer has been especially heartfelt because I was so invested in the outcome. I had argued and fought so many times to get an access and initiate dialysis, to get an extra-treatment, all this time being smugly self confident that I was helping the patient. Confident that I was fighting the good fight. Ughh.

So here it is, a review of the article that kicked me in the chest…
The objective was to determine if more intensive dialysis for acute kidney injury would improve survival in critically ill people. Unique to this trial, the protocol allowed patients to get either conventional hemodialysis or hemofiltration depending on the hemodynamic status of the patient at any time during the trial. This innovation allows the trial to better track actual practice. Additionally, it allows the trial to get past the eternal debate of which modality is better, and answer the question of what dose to target regardless of the modality.

The study was conducted from 2003 to 2007.

The trial was run at 27 institutions.

Enrollment criteria:

  • Critically ill adult
  • Age: 18 or older
  • Renal failure plus at least one other organ system failure or sepsis

Patients who were hemodynamically stable were provided hemodialysis (prescribed Kt/V 1.2-1.4). If they were unstable, CVVH or SLED was provided. The decision between CVVH and SLED was determined by individual site preference.

Patients were randomized to one of two dosing schemes:

Less-intensive strategy:

  • Stable: Intermittent hemodialysis: 3 days a week effluent
  • Unstable: Continuous therapy: effluent of 20 mL/kg/hr

Intensive strategy:

  • Stable: Intermittent hemodialysis: 6 days a week effluent
  • Unstable: Continuous therapy: effluent of 35 mL/kg/hr

These definitions for dose come from Ronco’s paper (continuous therapy) and Schiffl’s paper (intermittent therapy) two studies which are (were?) frequently invoked as support for high dose dialysis in acute kidney injury.

Dialysis was continued until recovery of renal function, discharge from the ICU or 28-days of therapy or death. Recovery of renal function was defined by 6-hour CrCl of >12 mL/min and investigator discretion or >20 mL/min.

Primary Endpoint: All-cause mortality at day 60.

Secondary endpoints:

  • In-hospital death
  • Recovery of renal function (CrCl>20). Recovery was defined as complete if Cr was <0.5>0.5 over the baseline creatinine.
  • Duration of renal replacement therapy
  • Dialysis free at 60 days
  • Duration of ICU stay
  • Return to previous home at day 60.

Power analysis

  • Estimated mortality with less-intensive strategy 55%
  • Estimated mortality with intensive strategy 45%

The authors estimated 10% loss to follow-up and all patients lost were assigned to “alive” for analysis. 90% power with a sample size of 1164.

Enrollment was below the power analysis goal of 1164 at 1124 but the study had better retention with 29 being lost for various reasons and 5 being lost and analyzed as “alive.” The power analysis anticipated 112 people being lost.


The all important table 1. shows a cohort that looks similar to the patients I take care of. 60% sepsis and 80% ventilated. Appache 26. All and all, a sick cohort.

The protocol was adhered to extremely well with extra treatments occurring on 0.5% of days in the high dose group and .5% of days with less-intensive strategy. Missed treatments occurred on 1.9% of days in the intensive strategy and 1.1% in less-intensive strategy. Surprisingly, the delivered dose of dialysis with intermittent therapy was a Kt/V of 1.3, right in the middle of the prescribed target. ICU patients are classically difficult to dialyze and previous analysis of delivered dose have shown it to lag well behind prescribed dose.

With continuous therapy the delivered dose like-wise correlated well with prescribed dose: 36.2 mL/kg with intensive strategy and 21.5 mL/kg with less-intensive strategy.

Primary outcome: 53.6% 60-day mortality with less-intensive strategy and 51.5% mortality with intensive strategy (p=0.47).

Secondary outcomes:

  • In-hospital mortality: 48.0% less-intensive strategy, 51.2% intensive strategy
  • Complete recovery of renal function (day 28): 18.4% less-intensive strategy, 15.4% intensive strategy
  • Return to home by day 60: 16.4% less-intensive strategy, 15.7% intensive strategy

Complications: Patients on the intensive strategy required vasopressor support during renal-replacement therapy more often, 14.4% vs 10.0% (p=0.02) and required interventions for hypotension more often, 37.7% vs 30.0% (p=0.006). However, in intermittent dialysis both groups reported similar rates of dialysis associated hypotension 18.5% with intensive vs 18.0% with less-intensive) and similar drops in blood pressure (MAP from 86 to 75 with intensive and from 86 to 74 with less-intensive). The increase in dialysis associated events maybe related to the increased frequency of dialysis (more exposures to dialysis) with intensive strategy.

Hypophosphatemia (17.6% vs 10.9%, p=0.001) and hypokalemia (7.5% vs 4.5%, p=0.03) were both more common with intensive therapy than with less-intensive therapy.

The editorial by Bonventre that was published with the article was okay. I would re-direct interested readers to the Hume, et al. editorial in AJKD which was better.

Some points from the Bonventre article include:

  • Increased numbers of men in the study
  • Lack of CKD patients
  • Questions about the changing of modalities allowed by the protocol
  • Increased amount of SLED in the intensive therapy group compared to the less-intensive strategy

Some choice quotations from the Hume article:

This report currently should be viewed as the definitive study defining dialysis dosing in critically ill patients with AKI.

During the maintenance phase of AKI, while hemodialysis/hemofiltration techniques are being utilized, the patient dies from multi-organ failure while in exquisite electrolyte and fluid balance.

Our group has focused on 2 major areas of evaluation. The first is the recognition that current renal substitution therapy only provides the small-solute clearance function of the kidney but not the metabolic and endocrine functions of the kidney. Similar to the clinical evidence that kidney transplantation markedly prolongs survival and improves health related quality of life compared to dialysis, the replacement of renal parenchymal cell functions in AKI may change the natural history of this disorder.

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Renal Vitamins

Just saw this post on the Renal Fellow’s Network. I appreciate his flippant attitude toward renal vitamins as they are so routine as to invite disregard but they may have an effect on mortality.

This 2004 article based on the DOPPS database shows a significant reduction in mortality (RR 0.84) associated with use of water soluble vitamins.


I always have a healthy skepticism for DOPPS data as they have been on the wrong side of the anemia, Kt/V and statin debate. Each time being refuted by the RCT. But I’ll take the position that since no one will ever do a randomized controlled trial we should go forward with the renal vitamins.

I first heard about this data on renal vitamins during the at the Easterling Lecture given by Eric Young for the Michigan NKF in 2003. At the time this was explained by the reduction of homocysteine induced by the folate in the vitamin. Since that has also fallen to the blade of the RCT, I wonder what componant of the renal vitamin explains the benefit.

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Journal Club: Aspirin and FGF-23

The first article was an intriguing look at various renal function parameters and how they respond to various doses of aspirin. All the patients were pre-treated with enalepril and a thiazide diuretic for 6 days. Then they were given one of four doses of aspirin:

  1. placebo
  2. 80 mg
  3. 160 mg
  4. 320 mg

They found decreased GFR, decreased sodium clearance, decreased solute clearance and decreased free water clearance with 160 mg and 320 mg but the effect was transient with all factors returning to baseline 4 hours after the aspirin was administered.

The article has a long introduction and discussion outlining all of the heart failure studies which have shown that aspirin can be harmful or can decrease the effectiveness of ACEi in heart failure.

The study is small (n=16, with each participant randomized to two doses of aspirin with a 2 week washout between doses) and the authors fail to fully describe the cohort. The primary weakness is the authors want to extrapolate there findings over 6 hours to the effect of aspirin taken chronically for years. Additionally they make the leap of using aspirin-induced changes in renal function to be a proxy for interference with ACEi effect on heart failure survival.

Nonetheless it will change the way I practice. I had previously given my patients (who essentially all are on diuretics and ACEi) the green light to take aspirin any way they want. I will now suggest they limit themselves to 81 mg for CAD protection.

The second article was the NEJM article on FGF-23 and the risk of mortality in hemodialysis patients. FGF-23, or fibroblast growth factor-23, is a newly discovered molecule which regulates the phosphorous in the body. It is one of the primary phosphatonins, signals which increase the renal excretion of phosphorous. Additionally they suppress 1-alpha hydroxylase lowering the amount of 1,25 dihydroxy-vitamin D.

This is prospective cohort with nested case-control of incident dialysis patients in the U.S. The investigators looked at 200 patients who died (cases) in the first year and compared them to 200 patients who survived one year (control). FGF-23 was measured on the first day of dialysis. They divided the cohort into quartiles based on phosphorous and found that patients who subsequently died had increased FGF-23. They found a graded increase in the risk of death with increased FGF-23 level that was signifigant in the whole cohort and inevery quartile of phosphorous except the highest.They also showed a dose responce of mortality to FGF-23 levels in the whole cohort in the crude data, case-mix adjusted and multivariate adjusted.


The authors in the discussion point out that the association of FGF-23 with mortality is stronger than that found with phosphorous and mortality. They found FGF-23 levels were 22% lower in African-Americans than in Caucasians. The authors leave a tease that this lower level of FGF-23 level may explain the improved survival found in African Americans on dialysis.