NephMadness: Sweet 16 – Collecting Tubule Region
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Collecting Tubule Region: Principal Cell Finalists:
(1) MDRD eGFR Equation vs (7) FeNa
MDRD eGFR Equation
The MDRD formula was published in 6-variable form in the Archives of Internal Medicine but the formula everyone uses is the 4-variable formula, strangely only presented in abstract form at 2000 Kidney Week (Levey et al, “A Simplified Equation To Predict Glomerular Filtration Rate from Serum Creatinine” Picture of the abstract book).
This oddity was corrected in 2006 when a slight modification of the equation was published for both the 4 variable and 6 variable formula. The modification made the equation accurate for newly standardized creatinine measurements.
The MDRD faced its child the CKD-EPI equation. This second generation equation is better validated, more representative and more accurate. That said the first round battle between Father and Son went much like Vader versus Luke in The Empire Strikes Back. Youth limped away, minus a hand. The reason MDRD wins is that the value that MDRD brought to nephrology didn’t depend on accuracy as much as ubiquity. By separating an estimate of GFR from weight, which was not available in automated laboratories, the MDRD formula allowed the automated reporting of GFR and helped spread the word of CKD as much as anything else.
In the round of 32, MDRD went against the 24-hour creatinine clearance in levey’s 1999 paper. This maybe the only matchup in the tournament where we can point to published data showing superiority of one team over another. Here the 24-hour creatinine clearance is less able to predict the GFR than the 6-variable MDRD equation. Keep your eyes on the R² value. An R² of 86.6% means that 86.6% of the variability seen in iothalamate GFRs (in this case) can be explained by the 24-hour creatinine clearance. A perfect test has an R² of 100% or 1.0.
It’s hard to believe that a single measured creatinine BUN and albumin, combined with age, gender and race are a better predictor of GFR than a 24-hour creatinine collection and serum creatinine. However, even though the MDRD bests 24-creatinine clearance, it is important not to throw away this tool. Patients whose body size dramatically differs from the norm can get more accurate measure of kidney function with the 24-hour creatinine clearance.
Fractional excretion of sodium (FeNa) went up against the fractional excretion of urea (FeUrea) in the first round. FeUrea was first described by Kohn and Kaplan in 1992. They pointed out that patients who have received diuretics, FeUrea was superior to the FeNa in determining if the patient was indeed volume depleted. However the data was retrospective and the timing between the diuretic administration and urine collection varied widely making the association less certain. FEUrea remained quiet for another decade. The test resurfaced in 2002 when Carvounis put the test on the map with a well done study of 102 consecutive patients with AKI. FEUrea bested FENa in patients on diuretics and performed as well as FENa in patients not on diuretics. This is probably the high point in the history of FEUrea.
Pepin in 2007 found FENa to be superior with or without diuretics, though neither tool worked very well. In 2009 Lim found that FEUrea was useful in patient exposed to diuretics, but less specific and not as good in patients without diuretic exposure. Diskin examined the two tests and found the FEUrea to be much more effective in the presence of diuretics but not perform well with infection as this could interfere with urea excretion. With the spread of data, the old standard FENa was able to muscle past FEUrea in a highly contested first round. In the second round FENa faced Winter’s Formula. The problem with Winter’s formula is that it allows for the diagnosis of respiratory contribution to acid base. We’re nephrologists and not interested in the lungs (aside from its ability to oxygenate and correct acidosis). Victory to FENa. In a Michigan versus VCU style blow-out.
Collecting Tubule Region: Intercalated Cell Finalists:
(2) Kidney Biopsy vs (2) Kidney Transplant
Kidney biopsy and Kidney transplant, two seminal achievements in nephrology, one represents CURE and the the other TRUTH, two words used rarely in nephrology and in truth rarely in all of medicine. To pick the winner of the two we need to acknowledge not only their strengths, but their weaknesses. Lets look closer.
Kidney biopsy revolutionized the study of nephrology. Its use has been instrumental in research in understanding the,etiology, natural history, and prognosis of disease. It is used clinically in to diagnose and provide prognostic information. It has been instrumental in the discovery of new diseases. Even conditions we now diagnose clinically we do so due to understanding brought from renal pathology. Standardization of biopsy specimens and readings has also allowed us to study therapeutic options in CKD and transplantation. A beautiful example of this is how the Banff classification changed the way we think about rejection and allowed further delineation of chronic allograft nephropathy into specific entities such as transplant glomerulopathy and polyoma nephropathy.
Biopsies are invasive. Although the risk of serious bleeding is only 0.9% it has lead to physicians performing biopsies only when absolutely necessary. In addition biopsies are only useful early in the disease process. Once the kidneys are small there isn’t much to detect except for scarring. Even in transplant there is talk about biopsies being inadequate. Newer studies are looking at combining genomics with histopathology as a better way of diagnosing the causes of allograft rejection. In addition new biomarkers are attempting to diagnose conditions as varied as rejection, membranous nephropathy, acute tubular necrosis and FSGS without relying on pathology. Unfortunatly an emerging trend has been the loss of biopsies from the scope of nephrology practice, more and more nephrologists are relying on interventionists to do biopsies.
Kidney transplant is as close to a cure for kidney disease as you can get. Literature suggests 48–82% reduction in long-term mortality compared to patients on the waitlist. In fact, the best outcomes occur when patients are transplanted before reaching dialysis, though this data should be adjusted for lead-time bias. Transplant is a moving target with advances surgical such as laparascopic living donor nephrectomy, and immunologic advances such as everolimus and belatacept. Initially a treatment for only the young and healthy, transplantation has shown benefit in every age group and disease.
Although it’s the best treatment for kidney disease it is not quite a cure. Modern immunosuppression still has many problems. These include a higher rate of malignancy, opportunistic infections, and diabetes. Although short term graft survival is excellent, long term outcome has not kept pace and is only minimally improved. Antibodies as a cause of graft failure have eluded us until recent years, and we still have few good treatments for this.
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