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Nephrology calculators for the iPhone

I have three different medical calculators on my iPhone. Two of them I actually use and the third came bundled as part of a different program. I put each calculator through its paces and comment on the differences found in this generally commoditized market.

The three calculators are:

Mediquations was the first medical calculator on the iPhone platform. The author is a third-year medical student, Zack Mahdavi. I have spoken with him and he is a good guy. Since releasing the program in July 2008, he has repeatedly upgraded Mediquations at no additional charge to users. He has focused on adding new calculations to his program and Mediquations has acquired a truly stunning breadth of equations. He claims 201 equations ranging from A-a Oxygen Gradient to Winter for Metabolic Acidosis.

The program has grown large and takes awhile to get past the splash screen and into the functional calculator.

The program then displays a conventional alphabetical list of equations. You can alternatively sort them by categories. Mediquations allows you to bookmark a set of frequently used “Favorites” to easily get past the ton of equations provided.

The MDRD equation is the conventional 4-variable equation and is accurate.

Tapping on a numerical variable sends you to an easy to finger keypad.

Thoughtfully you can switch units on the fly by tapping the i above the units.

For Boolean data you just tap the variable and it gets checked.

Tapping “More Info” gives you the formula and usually a reference and sometimes some background data on how to interpret the calculation. For the MDRD, Mediquations references the Levey paper (PDF) from the Annals which describes the 6-variable, not the 4-variable formula. There is a link which takes you to the PubMed reference in Mediquation’s own web browser.

The execution of “More Info” is spotty. The fractional excretion of sodium gives the formula, a paragraph on how to use and interpret the formula, and a reference to a 1984 American Journal of Medicine article rather than the original Espinel article which introduced the formula or the Shrier paper which validated it. The FeNa info is much better than the FeUrea info which is limited to just the formula without a reference or any help interpreting the calculation. The TTKG falls in the middle with the formula, a short descriptive paragraph which correctly points out that the formula is only valid with a urine Na over 25 and urine osmolality over 300 but gives no guidance on how to interpret the results. Instead of a peer reviewed reference, Mediquations directs people to Wikipedia which, as of 3/2/09, also does not have the correct Halperin reference but does a pretty good job on guiding the reader on how to interpret the calculation.

Overall I give Mediquations three out of four stars. Mahdavi has focused on breadth (200+ formulas!) rather than making the core formulas easier to use and fully documenting those calculations with useful information.

QxMD publishes four different free calculators: Neph (iTunes link), Cards, GI, and HEME. Each calculator has the same equations but the opening screen just shows the namesake’s equations. To get to the other specialties you have to drill down to them. I like this solution to the avalanche of equations found in Mediquation.

Instead of having a favorites tab the equations you use most frequently are automatically added to the Recent list which allows you to generate the same functionality of a favorites list without the work. Nice.

The best feature of NephCalc is a feature called Question Flow. When you turn this on each variable you need to enter is prompted automatically. This significantly speeds data input. For example the data entry flow for Mediquations and the MDRD GFR is:

  1. Tap age
  2. Enter age
  3. Save age
  4. Tap cr
  5. Enter cr
  6. Save cr
  7. Tap African American
  8. Tap Female

For Nephro Calc it is:

  1. Enter age
  2. Save
  3. Enter Cr
  4. Save
  5. Enter African American
  6. Enter Female

It saves two steps and feels a lot more streamlined. Nice innovation.

The Info button leads to a page with interpretive information and a reference. QxMD choose the 2002 K/DOQI guidelines for CKD staging which is probably a great reference, since the 4-variable formula was never published in a peer reviewed journal. The K/DOQI guideline does a nice job of describing the MDRD formula.

The FeUrea information page gives good data on interpreting this calculation and references the KI article (PDF) which put FeUrea on the map rather than the Kaplan and Kohn article where the calculation was first published. I think that is appropriate. (Though it makes me a little sad to see Orly Kohn forgotten for what it is one of the coolest new things in clinical nephrology. Orly was one of my mentor’s at U of C where she runs the PD clinic and is one of the attendings that enriched my fellowship. I remember doing the KI article in journal club and she was in the room and was completely modest about us critiquing her formula.)

With the TTKG QxMD again shines with a good description of how to interpret the calculation, the equation and the correct Halperin reference but the link which promises the abstract doesn’t work.

Like Mediquations however, not every equation has informative “Info.” The osmolar gap simply states “No additional information is available for this topic.”

Overall, I think that Nephro Calc is the best clinical calculator for nephrology and its free. It is not perfect but its close enough to perfect, to be the calculator I recommend to students and fellows rotating with me.

MedMath is bundled as part of Epocrates (iTunes Link). One of the key differences with MedMath is that instead of going to individual pages for each variable all the variables are on one screen. This limits the screen space for a number pad and MedMath uses a non-standard keypad which is significantly smaller than the ones in Mediquation and Nephro Calc. I found it more difficult to tap in the correct numbers with my fingers. I wonder if this is cruft from MedMath being originally written for the PalmOS and stylus-based touch screens.

The MDRD equation pictured is the less often used 6-variable formula. Which means that unless you have the albumin and BUN you can’t calculate the GFR.

The calculated osmolality does not allow one to enter the alcohol level, an omission also found in NephCalc. Only Mediquations allows you to correct the calculated osmolality for ethanol.

For me, the MDRD equation is one of the killer features of a medical calculator so MedMath with its 6-variable silliness totally fails and is a non-starter.

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On to the consult service.

My favorite month and the month I dread.
The most stimulating and just the most.

I have two medical students and one fellow. Which is a particularly difficult combination to teach. You have students at the beginning their education and a fellow almost done with her formal training.

My fellow has already told me that she wants to focus on fluids and electrolytes which suits my interests perfectly. It also dovetails nicely with what medical students typically want to get out of a fourth year nephro rotation (especially after rank lists have been submitted).

My plan for the syllabus is:

  • Mon: Ca, Phos, metabolic bone disease (PDF or Zip file for Pages), more acid-base problems
  • Tues: Collectively use mind maps to describe renal physiology Continue to teach ABGs: Anion gap metabolic acidosis with gap-gap (delta gap) and osmolar gap (PDF or Zip file for Pages)
  • Wed: Mind the gap…osmotic gap, anion gap, stool osmolar gap, urinary anion gap Busy clinic, no time for any teaching
  • Thurs: presentation of outlines/abstract of end-of-the-month presentation, non-anion gap metabolic acidosis PowerPoint presentation.
  • Fri: Vacation (for me not the students)
  • Mon: Alcohol and its protean effects on electrolytes Did this March 6th
  • Tues: first student/fellow presentation
  • Wed-Fri: NKF Spring Clinical Meeting
  • Mon: second student/fellow presentation
  • Tues: third student/fellow presentation

It’s an ambitious plan. We’ll see how it goes.

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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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Fluid and Electrolyte lecture at Providence from Friday

Third in the series of interesting fluid and electrolyte cases.

I would add a slide on where I was going in potassium before the anorexia section.

SlideSpace botches the torn paper frames I used through out the lecture so if you have Keynote, download and look at the native file.

Here is a link to the Keynote file.

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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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Crowd Sourcing 100 day

This coming week is the 100th day of school.

As part of a school project all of the kids need to bring in a hundred of something. My son wanted a hundred paper airplanes. We made a couple of dozen and I had my lecture for the ER residents coming up. So passed out two sheets of paper for each resident when I passed out the handout and I asked each resident to make a couple of airplanes. It turned out great.

Thanks St John ER Residents.

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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.