www.jasn.

org EDITORIALS

stem cell data are significant because they suggest that un- Critical Care Nephrology: Its
differentiated ES cells are also capable of contributing to
regeneration by providing the missing 3(IV) chain in a Not Just Acute Kidney Injury
manner similar to the blood and BM cells.
Although the successful treatment of mice, including in- Paul M. Palevsky* and Steven D. Weisbord*
*Renal Section and Center for Health Equity Research and Promo-
creased survival rates, is significant, it is still a big step to use tion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania;
such stem cells in clinical trials. This article, however, repre- and Renal Electrolyte Division, Department of Medicine, University
sents significant movement toward the development of cell- of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
based therapies for the treatment of kidney disease and has J Am Soc Nephrol 20: 22812282, 2009.
implications beyond Alport syndrome. doi: 10.1681/ASN.2009080875

DISCLOSURES The care of the critically ill with kidney disease represents a
None. growing proportion of patients treated by nephrologists in the
hospital. As a result, critical care nephrology, melding together
the expertise of nephrologists and intensivists, has emerged as
REFERENCES a distinct subdiscipline during the past decade.13 Critical care
nephrology is a topic at national and international meetings,
1. LeBleu V, Sugimoto H, Mundel TM, Gerami-Naini B, Finan E, Miller
has a proposed core curriculum for trainees,4 and even has its
CA, Gattone VH 2nd, Lu L, Shield CF 3rd, Folkman J, Kalluri R: Stem
cell therapies benefit Alport syndrome. J Am Soc Nephrol 20: 2359
own textbook5; however, a casual perusal of the literature in
2370, 2009 critical care nephrology rapidly reveals an almost exclusive fo-
2. Wang Z, Chamberlain JS, Tapscott SJ, Storb R: Gene therapy in cus on issues pertaining to acute kidney injury (AKI) with rel-
large animal models of muscular dystrophy. ILAR J 50: 187198, ative neglect of the patient with ESRD and superimposed crit-
2009
ical illness. In a nearly 1800-page textbook of critical care
3. Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen
R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy
nephrology, discussion of critically ill patients with ESRD are
A: piggyBac transposition reprograms fibroblasts to induced pluripo- covered in fewer than a dozen pages.5
tent stem cells. Nature 458: 766 770, 2009 The need for critical care nephrology to broaden its perspective
4. Ko JY, Lee HS, Park CH, Koh HC, Lee YS, Lee SH: Conditions for and provide increased focus on patients who have ESRD and are
tumor-free and dopamine neuron-enriched grafts after transplanting
critically ill is highlighted by the findings of Strijack et al. in this
human ES cell-derived neural precursor cells. Mol Ther July 14, 2009
[epub ahead of print]
issue of JASN.6 Using a prospectively maintained database of all
5. http://www.clinicaltrials.gov/ct2/results?termstemcells%2Ckidney. adult patients admitted to intensive care units (ICUs) in Win-
Accessed September 10, 2009 nipeg, Manitoba, Canada, they found patients with ESRD ac-
6. Sugimoto H, Mundel TM, Sund M, Xie L, Cosgrove D, Kalluri R: counted for nearly 3.4% of all ICU admissions and estimated the
Bone-marrow-derived stem cells repair basement membrane collagen
annual rate of ICU admission among adult patients with ESRD
defects and reverse genetic kidney disease. Proc Natl Acad Sci U S A
103: 73217326, 2006
was more than 25 times that of the general adult population. The
7. Haller MJ, Viener HL, Wasserfall C, Brusko T, Atkinson MA, Schatz DA: ESRD patients were younger, less likely to be male, and more than
Autologous umbilical cord blood infusion for type 1 diabetes. Exp twice as likely to have diabetes as compared with the general ICU
Hematol 36: 710 715, 2008 population. Although rates of coronary artery disease were simi-
8. Rowland JW, Hawryluk GW, Kwon B, Fehlings MG: Current status of
lar, patients with ESRD had more than two-fold the rate of pe-
acute spinal cord injury pathophysiology and emerging therapies:
promise on the horizon. Neurosurg Focus 25: E2, 2008
ripheral vascular disease, were more likely to require ICU care for
9. Katayama K, Kawano M, Naito I, Ishikawa H, Sado Y, Asakawa N, nonsurgical disease, had more than double the rate of sepsis than
Murata T, Oosugi K, Kiyohara M, Ishikawa E, Ito M, Nomura S: Irradi- the general ICU population, and had substantially higher severity
ation prolongs survival of Alport mice. J Am Soc Nephrol 19: 1692 of illness scores, even after subtracting the renal component. The
1700, 2008
patients with ESRD composed nearly 40% of patients who re-
10. Kang JS, Wang XP, Miner JH, Morello R, Sado Y, Abrahamson DR,
Borza DB: Loss of alpha3/alpha4(IV) collagen from the glomerular
ceived renal replacement therapy (RRT). The remainder, repre-
basement membrane induces a strain-dependent isoform switch to senting patients with AKI, had even higher severity of illness
alpha5alpha6(IV) collagen associated with longer renal survival in scores with more than double the frequency of sepsis as compared
Col4a3/ Alport mice. J Am Soc Nephrol 17: 19621969, 2006 with the patients with ESRD. Overall hospital mortality was ap-
11. Gross O, Borza DB, Anders HJ, Licht C, Weber M, Segerer S, Torra R,
Gubler MC, Heidet L, Harvey S, Cosgrove D, Lees G, Kashtan C,
Published online ahead of print. Publication date available at www.jasn.org.
Gregory M, Savige J, Ding J, Thorner P, Abrahamson DR, Antignac C,
Tryggvason K, Hudson B, Miner JH: Stem cell therapy for Alport The views expressed in this article are those of the authors and do not neces-
syndrome: the hope beyond the hype. Nephrol Dial Transplant 24: sarily represent the views of the Department of Veterans Affairs.
731734, 2009
Correspondence: Dr. Paul M. Palevsky, Room 7E123 (111F-U), VA Pittsburgh
Healthcare System, University Drive, Pittsburgh, PA 15240. Phone: 412-360-
3932; Fax: 412-360-6130; E-mail: [email protected]
See related article, Stem Cell Therapies Benefit Alport Syndrome, on pages
2359 2370. Copyright 2009 by the American Society of Nephrology

J Am Soc Nephrol 20: 22772284, 2009 Editorials 2281

 EDITORIALS www.jasn.org

proximately 10% in critically ill patients without ESRD or AKI, DISCLOSURES

16% in the patients with ESRD, and more than 40% in the pa- None.
tients with AKI. In contrast to patients with AKI, ESRD status was
not independently associated with mortality risk, and ICU length REFERENCES
of stay and resource use were similar to those of the overall ICU
population. ICU readmission rates, however, were approximately 1. Ronco C, Bellomo R, Feriani M, La Greca G: Critical care nephrology:
The time has come. Kidney Int Suppl 66: S1S2, 1998
twice as high in both the patients with ESRD and the patients with
2. Ronco C, Bellomo R: Critical care nephrology: The time has come.
AKI as in the general ICU population. Nephrol Dial Transplant 13: 264 267, 1998
This study confirms and extends the findings of previous stud- 3. Ronco C: Critical care nephrology: The journey has begun. Int J Artif
ies evaluating ICU use and outcomes in patients with ESRD.711 Organs 27: 349 351, 2004
The majority of past studies were small, single-center analyses 4. Liu KD: Critical care nephrology: Core curriculum 2009. Am J Kidney
Dis 53: 898 910, 2009
with limited inference to generalize. The only previous analysis of
5. Ronco C, Bellomo R, Kellum JA: Critical Care Nephrology, Philadel-
a large regional data set used the Intensive Care National Audit phia, Saunders, 2009
and Research Centre (ICNARC) Case Mix Programme database 6. Strijack B, Mojica J, Sood M, Komenda P, Bueti J, Reslerova M,
from Great Britain.11 This analysis found patients with ESRD Roberts D, Rigatto C: Outcomes of chronic dialysis patients admitted
composed 1.3% of all 276,731 admissions to 170 adult ICUs in to the intensive care unit. J Am Soc Nephrol 20: 24412447, 2009
7. Clermont G, Acker CG, Angus DC, Sirio CA, Pinsky MR, Johnson JP:
England, Wales, and Northern Ireland between 1995 and 2004.
Renal failure in the ICU: Comparison of the impact of acute renal
On the basis of the period prevalence of ESRD, the ICU use rate failure and end-stage renal disease on ICU outcomes. Kidney Int 62:
was approximately six admissions per 100 ESRD patient-years, a 986 996, 2002
rate slightly less than half that observed by Strijack et al.6 A variety 8. Dara SI, Afessa B, Bajwa AA, Albright RC: Outcome of patients with
of reasons may account for this, including differences in case mix, end-stage renal disease admitted to the intensive care unit. Mayo Clin
Proc 79: 13851390, 2004
criteria for ICU admission, and other ICU practice patterns as
9. Manhes G, Heng AE, Aublet-Cuvelier B, Gazuy N, Deteix P, Souweine
reflected by differences in age, frequency of nonsurgical ICU ad- B: Clinical features and outcome of chronic dialysis patients admitted
missions, and ICU and hospital mortality rates in both general to an intensive care unit. Nephrol Dial Transplant 20: 11271133, 2005
ICU and critically ill patients with ESRD. Although ESRD status 10. Uchino S, Morimatsu H, Bellomo R, Silvester W, Cole L: End-stage
was associated with an increased odds of in-hospital death (1.82; renal failure patients requiring renal replacement therapy in the inten-
sive care unit: Incidence, clinical features, and outcome. Blood Purif
95% confidence interval 1.13 to 1.37) in the ICNARC data set,
21: 170 175, 2003
after adjustment for demographics and case-mix factors, the odds 11. Hutchison CA, Crowe AV, Stevens PE, Harrison DA, Lipkin GW: Case
of death (1.24; 95% confidence interval 1.69 to 1.96) were mark- mix, outcome and activity for patients admitted to intensive care units
edly attenuated, suggesting that underlying comorbidity rather requiring chronic renal dialysis: A secondary analysis of the ICNARC
than renal failure per se was the major determinant of increased Case Mix Programme Database. Crit Care 11: R50, 2007
mortality risk in patients with ESRD.
See related article, Outcomes of Chronic Dialysis Patients Admitted to the
These data emphasize the need to include patients with ESRD Intensive Care Unit, on pages 24412447.
in the spectrum of critical care nephrology. Patients with ESRD
develop critical illness more frequently than the general popula-
tion and have a greater severity of illness than those without renal
disease. Moreover, patients with ESRD often present a unique set Allograft Biopsies: Studying
of clinical issues related to fluid and electrolyte management, min-
eral homeostasis, bleeding diatheses, and drug dosing that require
Them for All Theyre Worth
the multidisciplinary expertise of nephrologists and critical care
Isaac E. Stillman* and Martha Pavlakis
providers. Although renal failure seems to be, at most, only a mi-
*Department of Pathology, Renal Division, Department of Medicine,
nor contributor to the increased mortality risk associated with and Transplant Institute, Beth Israel Deaconess Medical Center, Bos-
critical illness in patients with ESRD, the simple fact remains: ton, Massachusetts; and Harvard Medical School, Boston,
Mortality in patients who have ESRD and develop critical illness is Massachusetts
unacceptably high. To improve the care and outcomes of critically J Am Soc Nephrol 20: 22822284, 2009.
ill patients with ESRD, practitioners and investigators need to doi: 10.1681/ASN.2009090930
broaden the focus of critical care nephrology to include this pa-
tient population. Advances in short-term renal allograft survival, as a result in
large part of the use of calcineurin inhibitors (CNIs), have not
ACKNOWLEDGMENTS
Published online ahead of print. Publication date available at www.jasn.org.
Dr. Weisbord is supported by a Department of Veterans Affairs, Vet- Correspondence: Dr. Isaac E. Stillman, Department of Pathology, Beth Israel
erans Health Administration, Health Services Research and Develop- Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Phone:
ment Service Career Development Transition Award and by Merit 617-667-4344; Fax: 617-667-7120; E-mail: [email protected]

Review Project IIR 07-190. Copyright 2009 by the American Society of Nephrology

2282 Journal of the American Society of Nephrology J Am Soc Nephrol 20: 22772284, 2009